What is RNA?

• RNA, short for Ribonucleic acid, is a crucial molecule involved in various biological processes related to the coding, decoding, regulation, and expression of genes. It is one of the nucleic acids, along with DNA, that play a fundamental role in the functioning of all known life forms. Together with lipids, proteins, and carbohydrates, nucleic acids are considered one of the four major macromolecules necessary for life.
• Similar to DNA, RNA is composed of chains of nucleotides. However, unlike DNA, RNA is typically found in a single-stranded form that can fold upon itself. Cellular organisms utilize messenger RNA (mRNA) to transmit genetic information, which is encoded using the nitrogenous bases guanine (G), uracil (U), adenine (A), and cytosine (C).
• RNA molecules serve active roles within cells, catalyzing biological reactions, controlling gene expression, and detecting and relaying responses to cellular signals. One of the primary functions of RNA is protein synthesis, a universal process where RNA molecules guide the synthesis of proteins on ribosomes. Transfer RNA (tRNA) molecules deliver amino acids to the ribosome, while ribosomal RNA (rRNA) links the amino acids together, forming the coded proteins.
• Nucleic acids are complex compounds composed of linear chains of monomeric nucleotides. Each nucleotide consists of phosphoric acid, sugar, and a nitrogenous base. Nucleic acids are vital in preserving, replicating, and expressing hereditary information. The two main types of nucleic acids are DNA and RNA.
• The discovery of nucleic acids is credited to Friedrich Miescher, a Swiss physician and biologist, who isolated a biological molecule from the nuclei of white blood cells in 1868. Initially named nuclein, the compound was later identified as DNA. The term “nucleic acid” was coined by Richard Altmann, a German pathologist, in 1889. During the early 1900s, RNA and DNA were not distinguished clearly and were referred to as nucleic acids. Eventually, the differences between RNA and DNA were recognized, such as the presence of ribose sugar in RNA and thymine being replaced by uracil.
• Francis Crick, along with James Watson, proposed the Central Dogma of Molecular Biology, which states that DNA leads to the formation of RNA, which then leads to protein synthesis. Different types of RNA involved in protein synthesis were subsequently identified, including mRNA, tRNA, and rRNA. These various RNA molecules have specific roles in the complex process of protein synthesis.

Definition of RNA

RNA, or Ribonucleic acid, is a nucleic acid molecule that plays a crucial role in gene expression and protein synthesis. It is a single-stranded molecule composed of nucleotides, including adenine (A), cytosine (C), guanine (G), and uracil (U). RNA carries genetic information from DNA and acts as a template for protein production in cells. It also participates in various cellular processes, including catalyzing reactions and regulating gene expression.

Difference between DNA and RNA – DNA vs RNA

• DNA
  • Full Name: Deoxyribonucleic Acid
  • Function: Replicates and stores genetic information
  • Structure: Double-stranded helix
  • Length: Longer polymers
  • Sugar: Deoxyribose
  • Bases: Adenine (A), Thymine (T), Guanine (G), Cytosine (C)
  • Base Pairs: A-T, C-G
  • Location: Nucleus, some in mitochondria
  • Reactivity: More stable, less reactive
  • UV Sensitivity: Vulnerable to UV damage
• RNA
  • Full Name: Ribonucleic Acid
  • Function: Converts genetic information and builds proteins
  • Structure: Single-stranded, sometimes forms secondary structure
  • Length: Shorter polymers
  • Sugar: Ribose
  • Bases: Adenine (A), Guanine (G), Cytosine (C), Uracil (U)
  • Base Pairs: A-U, C-G
  • Location: Nucleolus, cytoplasm
  • Reactivity: More reactive, less stable
  • UV Sensitivity: More resistant to UV damage

Characters	DNA	RNA
Full Name	Deoxyribonucleic Acid	Ribonucleic Acid
Function	Replicates and stores genetic information	Converts genetic information and builds proteins
Structure	Double-stranded helix	Single-stranded, sometimes forms secondary structure
Length	Longer polymers	Shorter polymers
Sugar	Deoxyribose	Ribose
Bases	Adenine (A), Thymine (T), Guanine (G), Cytosine (C)	Adenine (A), Guanine (G), Cytosine (C), Uracil (U)
Base Pairs	A-T, C-G	A-U, C-G
Location	Nucleus, some in mitochondria	Nucleolus, cytoplasm
Reactivity	More stable, less reactive	More reactive, less stable
UV Sensitivity	Vulnerable to UV damage	More resistant to UV damage

Structure of RNA

• RNA, like DNA, is a long polymer composed of nucleotides. However, there are several key differences in the structure of RNA that set it apart from DNA. RNA is a single-stranded helix, and it has a 5′ end with a phosphate group and a 3′ end with a hydroxyl group. The ribonucleotides in RNA are linked together by 3′ –> 5′ phosphodiester bonds. The nitrogenous bases found in RNA include adenine (A), cytosine (C), uracil (U), and guanine (G).
• One of the primary distinctions between RNA and DNA is the presence of uracil in RNA instead of thymine. Uracil, like thymine, can form base pairs with adenine. Additionally, RNA contains ribose sugar, whereas DNA contains deoxyribose sugar. The corresponding ribonucleosides in RNA are adenosine, guanosine, cytidine, and uridine. These ribonucleosides can be further phosphorylated to form ribonucleotides such as adenosine 5’-triphosphate (ATP), guanosine 5’-triphosphate (GTP), cytidine 5’-triphosphate (CTP), and uridine 5’-triphosphate (UTP).
• Each nucleotide in RNA consists of a ribose sugar, with carbons numbered from 1′ to 5′. The 1′ position of the ribose sugar is attached to a base, which can be adenine, cytosine, guanine, or uracil. Phosphate groups are attached to the 3′ position of one ribose and the 5′ position of the next ribose, forming a chain. The negative charges on the phosphate groups make RNA a charged molecule.
• RNA can form various secondary structures due to its ability to fold upon itself. The presence of a hydroxyl group at the 2′ position of the ribose sugar contributes to the A-form geometry of the RNA helix, although it can occasionally adopt the B-form geometry observed in DNA. The A-form geometry results in a deep and narrow major groove and a shallow and wide minor groove. RNA can form hydrogen bonds between cytosine and guanine, adenine and uracil, and guanine and uracil. Other interactions, such as bulges and base-pairing in specific motifs like the GNRA tetraloop, are also possible.
• RNA undergoes various modifications as it matures. Pseudouridine (Ψ) and ribothymidine (T) are modified bases found in RNA, while inosine (I) plays a role in the wobble hypothesis of the genetic code. There are over 100 naturally occurring modified nucleosides in RNA, with tRNA containing the greatest structural diversity of modifications. The specific functions of many of these modifications are not fully understood, but they are often found in functional regions of RNA molecules.
• Just like proteins, RNA molecules require specific tertiary structures to function properly. Secondary structural elements, such as hairpin loops, bulges, and internal loops, contribute to the overall folding of RNA. Metal ions like Mg2+ are often needed to stabilize these secondary and tertiary structures due to the charged nature of RNA. The naturally occurring enantiomer of RNA is D-RNA, composed of D-ribonucleotides. However, L-RNA can be synthesized using L-ribose or L-ribonucleotides, and it is more stable against degradation by RNase.
• The topology of a folded RNA molecule can be defined based on the arrangement of intra-chain contacts within the RNA. This topology is often referred to as circuit topology and is similar to the concept of protein folding. By understanding the structure and topology of RNA, scientists can gain insights into its biological functions and design RNA molecules for specific purposes.

Structure of RNA Summery

• RNA is a single-stranded helix.
• It consists of ribonucleotides linked together by 3′ –> 5′ phosphodiester bonds.
• The bases in RNA are adenine (A), cytosine (C), uracil (U), and guanine (G).
• Uracil replaces thymine in RNA, and it can form base pairs with adenine.
• RNA contains ribose sugar instead of deoxyribose sugar found in DNA.
• The corresponding ribonucleosides in RNA are adenosine, guanosine, cytidine, and uridine.
• Each nucleotide in RNA has a ribose sugar with carbons numbered from 1′ to 5′.
• A base is attached to the 1′ position, which can be A, C, G, or U.
• Phosphate groups are attached to the 3′ position of one ribose and the 5′ position of the next.
• RNA can adopt A-form geometry, with a deep major groove and a shallow minor groove.
• Hydrogen bonds can form between cytosine and guanine, adenine and uracil, and guanine and uracil.
• RNA undergoes modifications, such as pseudouridine (Ψ), ribothymidine (T), and inosine (I).
• There are over 100 naturally occurring modified nucleosides in RNA.
• RNA requires metal ions like Mg2+ to stabilize secondary and tertiary structures.
• The naturally occurring enantiomer of RNA is D-RNA, but L-RNA can be synthesized.
• RNA has a defined topology based on intra-chain contacts, known as circuit topology.
• Understanding RNA structure and topology is essential for its biological functions and design purposes.

Nucleic acid components:

• Nucleobase: nitrogenous base ( adenine )
• Nucleoside: nitrogenous base + sugar ( adenosine)
• Nucleotide: nitrogenous base + sugar + phosphate (adenosine monophosphate)
• Nucleic acid: polymer of nucleotide (RNA)

Secondary Structure of RNA

• The secondary structure of RNA refers to the local folding of the RNA molecule, involving base pairing interactions between nucleotides within the same strand. While most RNA molecules are single-stranded, they can contain regions that can form complementary base pairs, leading to the formation of double-stranded regions.
• Certain types of RNA, such as ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), exhibit significant secondary structure. These molecules fold into intricate three-dimensional shapes, facilitated by the formation of base pairs between complementary nucleotides. The secondary structure of rRNAs plays a crucial role in the formation of the ribosome, the cellular machinery responsible for protein synthesis. tRNAs also rely on their secondary structure to interact with amino acids and deliver them to the ribosome during translation.
• Additionally, some messenger RNAs (mRNAs) can adopt secondary structures. These structures can affect various aspects of mRNA function, such as stability, translation efficiency, and regulation. Secondary structure elements within mRNAs can influence the binding of proteins and other molecules involved in gene expression.
• The secondary structure of RNA is often visualized using diagrams, such as dot plots or secondary structure prediction algorithms. These representations illustrate the base pairing interactions within the RNA molecule, providing insights into its folding patterns. Experimental techniques, such as chemical probing and RNA structure mapping, can also be employed to study the secondary structure of specific RNA molecules.
• Understanding the secondary structure of RNA is important because it contributes to the overall function and behavior of these molecules. The formation of specific secondary structures is crucial for proper RNA folding, stability, interactions with other molecules, and the execution of their biological roles within the cell.

Types of RNA

The three major types of RNAs with their respective cellular composition are given below

1. Messenger RNA (mRNA) : 5–10%
2. Transfer RNA (tRNA) : 10–20%
3. Ribosomal RNA (rRNA) : 50–80%

1. Messenger RNA (mRNA)

Messenger RNA (mRNA) is a single-stranded molecule of RNA that plays a crucial role in protein synthesis. Here are key points about mRNA:

• mRNA is generated through the process of transcription. An enzyme called RNA polymerase converts the gene sequence in DNA into a primary transcript mRNA, also known as pre-mRNA.
• Pre-mRNA contains both introns and exons. Introns are non-coding regions that are removed through RNA splicing, leaving only the exons, which encode the protein sequence. This processing step results in the formation of mature mRNA.
• The sequence of nucleotides in mRNA carries the genetic information, arranged in codons consisting of three ribonucleotides each. Codons specify the amino acids that will be incorporated into the protein during translation.
• The translation of codons into amino acids requires the participation of other types of RNA. Transfer RNA (tRNA) recognizes the codons on mRNA and delivers the corresponding amino acids to the ribosome. Ribosomal RNA (rRNA) is a crucial component of the ribosome, the cellular machinery responsible for protein synthesis.
• Mature mRNA is read by the ribosome during translation, where it serves as a template for protein synthesis. The ribosome moves along the mRNA, reading each codon and assembling the amino acids carried by tRNA into a polypeptide chain.
• The flow of genetic information from DNA to mRNA to protein is known as the central dogma of molecular biology.
• The name “messenger RNA” was coined by François Jacob and Jacques Monod, and it was first identified and described independently by teams led by Sydney Brenner, Francis Crick, and James Watson in the early 1960s.
• mRNA molecules are long, single-stranded polymers composed of nucleotides linked by phosphodiester bonds. They contain four nitrogenous bases: adenine (A), guanine (G), cytosine (C), and uracil (U), with uracil replacing thymine (T) found in DNA.
• Mature mRNA consists of various regions, including the 5′ cap (a methyl guanosine triphosphate cap at the 5′-end), the 5′ untranslated region (UTR), the coding region (comprising codons for protein synthesis), the 3′ UTR, and the poly(A) tail (a string of adenine nucleotides added to the 3′-end).
• mRNA can be monocistronic, coding for a single protein, as commonly observed in eukaryotic mRNAs. In contrast, prokaryotic mRNAs are often polycistronic, encoding multiple proteins that are functionally related and regulated by a shared promoter and operator regions.
• The mitochondrial genome in humans is an example of a polycistronic mRNA.

mRNA serves as a crucial intermediary in the flow of genetic information, enabling the synthesis of proteins based on the instructions encoded in DNA.

Properties of mRNA

Messenger RNA (mRNA) exhibits several important properties that contribute to its role in protein synthesis and gene expression. Here are some key properties of mRNA:

1. Single-stranded: mRNA is a single-stranded molecule, unlike DNA, which consists of a double helix. This single-stranded nature allows mRNA to interact with other molecules and undergo various processes involved in protein synthesis.
2. Transcription product: mRNA is synthesized through the process of transcription, where an enzyme called RNA polymerase converts the DNA template into RNA. It carries the genetic information encoded in the DNA and serves as a transcript of a specific gene.
3. Variable length: The length of mRNA molecules can vary depending on the gene being transcribed. Some mRNA molecules are relatively short, while others can be quite long, encompassing thousands of nucleotides.
4. Genetic code: The genetic information in mRNA is encoded in the sequence of nucleotides. Nucleotide triplets, called codons, specify the incorporation of specific amino acids during protein synthesis. The genetic code is universal, meaning that the same codons code for the same amino acids across different organisms.
5. Template for protein synthesis: mRNA serves as a template during translation, the process by which proteins are synthesized. Ribosomes read the sequence of codons on mRNA and translate them into the corresponding amino acids, ultimately leading to the synthesis of a specific protein.
6. 5′ cap: Mature mRNA molecules typically possess a modified nucleotide, known as the 5′ cap, at their 5′-end. The 5′ cap protects the mRNA from degradation, facilitates its export from the nucleus to the cytoplasm, and aids in the recognition and binding of the mRNA by ribosomes during translation.
7. Poly(A) tail: Another characteristic feature of mature mRNA is the addition of a polyadenylate (poly(A)) tail at the 3′-end. This tail consists of a string of adenine nucleotides and plays a role in mRNA stability, nuclear export, and efficient translation.
8. Splicing and alternative splicing: In many eukaryotic genes, pre-mRNA undergoes a process called RNA splicing, where introns (non-coding regions) are removed, and exons (coding regions) are joined together. This splicing process allows for the production of multiple mRNA isoforms from a single gene, through a mechanism known as alternative splicing.
9. Transient nature: mRNA is generally a transient molecule, meaning that its lifespan within the cell is limited. The stability of mRNA varies depending on factors such as its sequence, the presence of regulatory elements, and cellular conditions. mRNA molecules are continuously synthesized and degraded as part of the dynamic regulation of gene expression.
10. Regulation of gene expression: mRNA plays a crucial role in the regulation of gene expression. Various mechanisms control the abundance, stability, and translation efficiency of mRNA molecules, thereby influencing the levels of specific proteins within the cell. This regulation allows for precise control of gene expression in response to developmental, environmental, and physiological cues.

These properties of mRNA contribute to its role as a key intermediary molecule in the central dogma of molecular biology and highlight its significance in gene expression and protein synthesis.

Function of mRNA

The function of mRNA (messenger RNA) is primarily to serve as a template for protein synthesis. It carries the genetic information from the DNA in the nucleus to the ribosomes, where it is translated into a sequence of amino acids to form a polypeptide chain, ultimately leading to the synthesis of proteins. Here are some key points about the function of mRNA:

1. Protein synthesis: The primary role of mRNA is to convey the genetic information encoded in DNA to the ribosomes, where proteins are synthesized. During transcription, RNA polymerase synthesizes mRNA using the DNA template. The mRNA molecule carries the information in its nucleotide sequence, with each three-nucleotide codon specifying a specific amino acid.
2. Template for translation: mRNA provides the template for translation, the process by which ribosomes read the mRNA sequence and synthesize proteins. Ribosomes bind to the mRNA and move along its sequence, matching each codon with the corresponding amino acid carried by transfer RNA (tRNA). This ensures that the correct sequence of amino acids is incorporated into the growing polypeptide chain.
3. Genetic code: The sequence of nucleotides in mRNA is read in sets of three, known as codons. Each codon specifies a particular amino acid or serves as a stop signal, indicating the end of protein synthesis. The genetic code is universal, meaning that the same codons code for the same amino acids across different organisms.
4. mRNA vaccines: Recent advancements in mRNA technology have led to the development of mRNA vaccines, such as the Pfizer-BioNTech and Moderna COVID-19 vaccines. In these vaccines, modified mRNA sequences encoding viral antigens are delivered to cells, triggering the production of these antigens and initiating an immune response. mRNA vaccines offer a flexible and efficient method for generating immune responses against specific pathogens.
5. Therapeutic applications: mRNA-based therapies have shown promise in treating various diseases. By delivering modified mRNA sequences to cells, specific proteins can be produced to treat diseases directly or trigger desired cellular responses. mRNA therapies are being investigated for cancer, autoimmune diseases, metabolic disorders, and respiratory inflammatory conditions. Additionally, mRNA can be used in gene editing techniques like CRISPR to induce cells to produce the desired proteins.

The function of mRNA as a template for protein synthesis and its ability to be modified and delivered to cells make it a powerful tool in both understanding biological processes and developing novel therapies for various diseases. The recent success of mRNA-based vaccines highlights the significant potential of mRNA in the field of medicine.

2. rRNA (Ribosomal RNA)

Ribosomal RNA (rRNA) is a type of RNA found in ribosomes, the cellular structures responsible for protein synthesis. Here are some key points about rRNA:

• Abundance in cells: rRNA constitutes a significant portion of the total RNA present in a cell, accounting for about 80% of the RNA content. This high abundance reflects the crucial role of rRNA in ribosome structure and function.
• Ribosome composition: Ribosomes are composed of two major subunits—the small ribosomal subunit and the large ribosomal subunit. These subunits contain rRNA molecules along with ribosomal proteins. The small subunit reads the mRNA, while the large subunit joins amino acids to form a polypeptide chain during protein synthesis.
• Types of rRNA: There are different types of rRNA molecules present in ribosomes, including small rRNAs and large rRNAs. The small rRNA molecules are found in the small ribosomal subunit, while the large rRNA molecules are present in the large ribosomal subunit. These rRNA molecules play crucial roles in ribosome assembly and protein synthesis.
• Ribosome formation: rRNA combines with proteins in the cytoplasm to form ribosomes. These ribosomes serve as the sites of protein synthesis within the cell and contain the necessary enzymes for this process. The rRNA molecules within the ribosomes interact with mRNA and other molecules required for protein synthesis.
• Catalytic activity: rRNA exhibits catalytic activity and is considered a ribozyme. It catalyzes the formation of peptide bonds between amino acids during protein synthesis. The three-dimensional structure of the rRNA core influences the overall structure of the ribosome, and ribosomal proteins help maintain this structure and contribute to ribosome function.
• Nucleolar synthesis: The synthesis of rRNA occurs in specific structures within the nucleus called nucleoli. Nucleoli are dense, spherical structures where rRNA-coding genes are transcribed. These structures play a vital role in the production and assembly of ribosomes by retaining ribosomal proteins.

Ribosomal RNA plays a fundamental role in protein synthesis by providing the structural and catalytic components necessary for ribosome function. Its abundance and involvement in ribosome assembly make it a critical component of cellular processes related to gene expression and protein production.

Properties of rRNA

Here are some properties of ribosomal RNA (rRNA):

1. Abundance: rRNA is the most abundant type of RNA in cells, comprising approximately 80% of the total RNA content. This high abundance reflects the crucial role of rRNA in ribosome structure and function.
2. Structural Role: rRNA plays a central role in the structure of ribosomes. It combines with ribosomal proteins to form the two major subunits of ribosomes—the small ribosomal subunit and the large ribosomal subunit. These subunits come together during protein synthesis to create the functional ribosome.
3. Catalytic Activity: Certain regions of rRNA exhibit catalytic activity, acting as ribozymes. They facilitate the formation of peptide bonds between amino acids during protein synthesis. This catalytic activity underscores the important role of rRNA in the ribosome’s ability to synthesize proteins.
4. Conservation: rRNA is highly conserved across different species. The sequences and structures of rRNA molecules show remarkable similarity between organisms, indicating their evolutionary importance and functional significance in protein synthesis.
5. Non-Coding RNA: While rRNA itself is not translated into proteins, it serves as a critical component of ribosomes, the cellular machinery responsible for protein synthesis. rRNA acts as a scaffold and provides the structural framework necessary for ribosome assembly and function.
6. Modification: rRNA molecules undergo various modifications after transcription. These modifications include methylation, pseudouridylation, and base modifications. These alterations can affect the stability, folding, and functionality of rRNA, ultimately impacting ribosome function and protein synthesis.
7. Variability: Different organisms have variations in the size and composition of rRNA. For example, bacterial rRNA is smaller and structurally distinct from eukaryotic rRNA. These differences reflect the diverse evolutionary paths and adaptations of organisms in protein synthesis.
8. Evolutionary Studies: rRNA has been widely used in molecular biology research for phylogenetic analysis and evolutionary studies. Comparing the sequences of rRNA from different organisms allows scientists to infer evolutionary relationships and construct phylogenetic trees.

Ribosomal RNA is a fundamental component of ribosomes and plays a vital role in protein synthesis. Its abundance, conservation, catalytic activity, and structural properties make rRNA essential for the efficient and accurate translation of genetic information into proteins.

Function of rRNA-Ribosomal RNA

The primary function of ribosomal RNA (rRNA) is to facilitate protein synthesis, which is carried out by ribosomes in the cell. Here are the key points regarding the function of rRNA:

• Translation Initiation: rRNA plays a crucial role in the initiation of translation. It helps in the assembly of ribosomes on the mRNA molecule by binding to messenger RNA (mRNA) and other components involved in protein synthesis.
• Binding Sites: The three binding sites within the ribosome, namely the A (aminoacyl) site, P (peptidyl) site, and E (exit) site, are created by the three-dimensional structure of rRNA. These sites accommodate transfer RNA (tRNA) molecules, ensuring the accurate translation of mRNA codons into amino acids.
• Protein Synthesis: rRNA participates in the actual process of protein synthesis. It interacts with both mRNA and tRNA to facilitate the decoding of mRNA codons by tRNAs carrying the corresponding amino acids. It positions the tRNAs within the ribosome, allowing the formation of peptide bonds between amino acids and the elongation of the polypeptide chain.
• Catalytic Activity: Certain regions of rRNA exhibit catalytic activity, acting as ribozymes. They catalyze the formation of peptide bonds between amino acids during protein synthesis, making rRNA an essential component for the ribosome’s enzymatic function.
• Antibiotic Binding Sites: Bacterial rRNA contains specific binding sites for antibiotics, such as streptomycin and tetracycline. These antibiotics can interact with bacterial rRNA, disrupting the normal functioning of ribosomes and inhibiting protein synthesis. Understanding these interactions has led to the development of antibiotics to combat bacterial infections.
• Evolutionary Conservation: rRNA sequences and structural elements are highly conserved across different species. This conservation reflects the crucial role of rRNA in protein synthesis and its fundamental importance in cellular processes. The conserved regions serve as the catalytic sites and maintain the overall structure of the ribosome.
• Polysomes: Multiple ribosomes can simultaneously translate a single mRNA molecule, forming a polysome. This allows for efficient and rapid protein synthesis, increasing the cell’s capacity to produce proteins.
• Additional Roles: Studies have linked rRNA to other cellular processes. For example, precursor rRNA has been associated with the production of microRNAs, which are involved in regulating gene expression and various cellular functions.

3. tRNA – Transfer RNA

Transfer RNA (tRNA) is a crucial molecule involved in protein synthesis. Here are the key points about tRNA:

• Structure and Function: tRNA is an adapter molecule composed of RNA, typically 76 to 90 nucleotides long in eukaryotes. It acts as a physical link between messenger RNA (mRNA) and the amino acid sequence of proteins. Each tRNA molecule carries a specific amino acid and recognizes the corresponding codon on the mRNA during translation.
• Anticodon and Codon Recognition: The tRNA molecule contains a three-nucleotide sequence called the anticodon, which is complementary to the codon on the mRNA. The anticodon base pairs with the codon in mRNA, ensuring accurate translation of the genetic code into the correct amino acid sequence.
• Amino Acid Attachment: At the opposite end of the tRNA molecule is the attachment site for the specific amino acid that corresponds to the anticodon sequence. Aminoacyl tRNA synthetases are enzymes responsible for catalyzing the covalent attachment of the correct amino acid to the tRNA molecule.
• Diversity of tRNA: Different types of tRNA molecules exist, each specific to one type of amino acid. Since multiple codons can code for the same amino acid, there are several tRNA molecules with different anticodons but carrying the same amino acid.
• Chemical Modifications: tRNA molecules undergo various chemical modifications, such as methylation or deamidation, which can occur at several nucleotides. These modifications can affect the interaction between tRNA and ribosomes and can influence the base-pairing properties of the anticodon.
• Protein Synthesis Process: During protein synthesis, tRNA molecules with attached amino acids are delivered to the ribosome by elongation factors. The ribosome facilitates the transfer of the growing polypeptide chain from the tRNA attached to its 3′ end to the amino acid attached to the newly delivered tRNA. This process occurs in the ribosome’s active site and is catalyzed by the ribosome itself.
• Role in Translation: tRNA acts as an essential component of translation, which is the process of synthesizing proteins based on the genetic code carried by mRNA. It ensures the accurate pairing of codons and anticodons, facilitating the incorporation of the correct amino acids into the growing polypeptide chain.

Overall, tRNA plays a crucial role in protein synthesis by carrying specific amino acids to the ribosome and accurately interpreting the genetic code carried by mRNA. Its structural features, including the anticodon and amino acid attachment site, enable it to recognize and decode the mRNA codons, allowing for the precise assembly of proteins according to the genetic instructions.

Properties of tRNA – Transfer RNA

Transfer RNA (tRNA) possesses several properties that contribute to its essential role in protein synthesis. Here are the key properties of tRNA:

• Cloverleaf Structure: tRNA molecules exhibit a distinctive cloverleaf-shaped structure. It consists of four stem-loop regions designated as the acceptor stem, D loop, anticodon loop, and TΨC (thymine, pseudouridine, cytosine) loop. This structure allows tRNA to carry out its functions in protein synthesis.
• Anticodon: The anticodon loop contains a three-nucleotide sequence that is complementary to the codon on the mRNA. The anticodon enables tRNA to recognize and bind to the appropriate codon during translation, ensuring the accurate pairing of codons and anticodons.
• Amino Acid Attachment Site: At the 3′ end of tRNA, there is a specific site where the corresponding amino acid is attached. Aminoacyl tRNA synthetases catalyze the specific attachment of the correct amino acid to the tRNA molecule, ensuring that each tRNA carries the appropriate amino acid.
• Genetic Code Specificity: Each tRNA molecule is specific to a particular amino acid and recognizes only the codons that correspond to that amino acid. This specificity is crucial for the accurate translation of the genetic code, as it ensures that the correct amino acids are incorporated into the growing polypeptide chain.
• Wobble Base Pairing: The pairing between the third nucleotide of the codon and the first nucleotide of the anticodon is more flexible, allowing for non-standard base pairing. This phenomenon is known as wobble base pairing and allows a single tRNA to recognize multiple codons with slight variations, enhancing the efficiency of protein synthesis.
• Post-Transcriptional Modifications: tRNA molecules undergo extensive post-transcriptional modifications, such as base modifications and nucleotide additions. These modifications can impact the stability, structure, and functionality of tRNA, ensuring its proper folding and interaction with the ribosome during translation.
• Structural Flexibility: tRNA molecules exhibit structural flexibility due to the presence of single-stranded regions and flexible linkers between the stem-loop structures. This flexibility enables tRNA to adopt different conformations during the protein synthesis process and interact with various components of the translation machinery.
• High Abundance: tRNA molecules are abundantly present in cells. They constitute a significant fraction of the cellular RNA and play a crucial role in protein synthesis, ensuring the continuous production of functional proteins.

Functions of tRNA – Transfer RNA

Transfer RNA (tRNA) has several important functions in the process of protein synthesis. Here are the key functions of tRNA:

1. Adapter Molecule: tRNA serves as an adapter molecule that links the genetic information encoded in mRNA to the amino acid sequence of proteins. Each tRNA molecule carries a specific amino acid and recognizes the corresponding codon on the mRNA through its anticodon region.
2. Aminoacylation: The first step in protein synthesis involves the aminoacylation of tRNA. This process is catalyzed by aminoacyl-tRNA synthetases, which attach the appropriate amino acid to the corresponding tRNA molecule, ensuring that each tRNA is correctly loaded with its specific amino acid.
3. Carrying Amino Acids: During the translation process, tRNA molecules transport amino acids to the ribosomal subunits, where protein synthesis occurs. The amino acid attached to the tRNA at its 3′ end is carried to the ribosome, ready to be added to the growing polypeptide chain.
4. Interaction with Ribosomes: tRNA interacts with the ribosomes, which are large complexes composed of ribosomal RNA (rRNA) and proteins. Within the ribosome, tRNA binds to the mRNA codons in the A (aminoacyl) site, bringing the corresponding amino acid in close proximity to the growing polypeptide chain.
5. Peptide Bond Formation: tRNA facilitates the formation of peptide bonds between amino acids in the ribosome. The ribosome catalyzes the transfer of the growing polypeptide chain from the tRNA in the P (peptidyl) site to the amino acid carried by the tRNA in the A site. This process continues sequentially, resulting in the elongation of the polypeptide chain.
6. Ribosomal Binding Sites: The ribosome has three binding sites for tRNA molecules. The A site (aminoacyl site) accommodates the incoming aminoacyl-tRNA carrying the next amino acid to be added to the polypeptide chain. The P site (peptidyl site) holds the tRNA attached to the growing polypeptide chain. The E site (exit site) temporarily holds the deacylated tRNA before it is released from the ribosome.
7. Codon Decoding: tRNA’s anticodon region base pairs with the corresponding codon on the mRNA, ensuring the accurate decoding of the genetic information. The specific pairing between the anticodon and codon determines which amino acid will be incorporated into the growing polypeptide chain.
8. Completion of Polypeptide Chain: The process of decoding codons of mRNA by specific tRNA molecules continues until the entire sequence for a polypeptide chain is translated. Each tRNA delivers its amino acid to the ribosome, allowing the ribosome to assemble the amino acids in the correct order to form the desired protein.

Types of RNA Based on Length

RNA can be classified into two main types based on its length: small RNA and long RNA.

1. Small RNA

Small RNAs are relatively short in length, typically shorter than 200 nucleotides (nt). They serve various regulatory functions within the cell. Examples of small RNAs include:

• 5.8S ribosomal RNA (rRNA): A component of the ribosome, involved in protein synthesis.
• 5S rRNA: Another component of the ribosome, contributing to its structure and function.
• Transfer RNA (tRNA): Transfers amino acids to the ribosome during protein synthesis.
• MicroRNA (miRNA): Regulates gene expression by binding to messenger RNAs (mRNAs), leading to their degradation or inhibition of translation.
• Small interfering RNA (siRNA): Mediates RNA interference, silencing specific genes by targeting and degrading complementary mRNAs.
• Small nucleolar RNA (snoRNAs): Guides chemical modifications of other RNA molecules, such as rRNA and tRNA.
• Piwi-interacting RNA (piRNA): Involved in silencing transposons and maintaining genome stability in germline cells.
• tRNA-derived small RNA (tsRNA): Derived from tRNA precursors and implicated in gene regulation.
• Small rDNA-derived RNA (srRNA): Derived from ribosomal DNA (rDNA) and potentially involved in ribosome biogenesis and regulation.

2. Long RNA

Long RNAs, also known as large RNAs, are generally greater than 200 nt in length. They often play important roles in gene regulation and cellular processes. The two major types of long RNAs are:

• Long non-coding RNA (lncRNA): These are transcribed RNA molecules that do not encode proteins. They have diverse functions, including gene regulation, chromatin remodeling, and scaffolding of molecular complexes.
• Messenger RNA (mRNA): mRNA carries the genetic information from DNA to the ribosome, where it is translated into proteins. They are generally the intermediates between genes and proteins.

It’s worth noting that while the majority of small RNAs and long RNAs fall into the aforementioned categories, there can be exceptions and additional subclasses depending on specific organisms and their unique RNA characteristics.

Other Types of RNA

In addition to its basic function in protein synthesis, RNA is also involved in post-transcriptional modification, DNA replication, and gene control. Certain kinds of RNA are exclusive to certain forms of life, such as eukaryotes or bacteria.

1. Small nuclear RNA (snRNA)

• snRNA is required for the maturation of pre-messenger RNA (pre-mRNA) into mature messenger RNA (mRNA). They are quite brief, averaging about 150 nucleotides in length.

2. Regulatory RNAs

• Several forms of RNA, including micro RNA (miRNA), small interfering RNA (siRNA), and antisense RNA, regulate gene expression (aRNA).
• microRNAs (21-22 nucleotides) are found in eukaryotes and function via RNA interference (RNAi).
• With the assistance of enzymes, miRNA is able to degrade complimentary mRNA. This can inhibit the translation of the mRNA or expedite its decay.
• siRNAs (20-25 nucleotides) are frequently created by the degradation of viral RNA, although there are additional endogenous sources of siRNAs. They operate similarly to microRNA.
• The 5′ untranslated region or 3′ untranslated region of an mRNA may contain regulatory elements, such as riboswitches; these cis-regulatory elements affect the activity of the mRNA.

a. MicroRNAs

• MicroRNAs (miRNA) are noncoding RNAs that primarily regulate genes.
• RNA polymerase II is responsible for transcribing them from the host gene into primary microRNA.
• They are then transformed into mature miRNA by endonucleases such as Drosha and Dicer. According to studies, miRNAs that bind to the 3′ untranslated region (3’UTR) of mRNAs inhibit translation, whereas miRNAs that bind to promoter regions stimulate transcription.
• miRNAs can also perform comparable functions to hormones.
• To regulate cellular activity, they are released into the extracellular fluid and taken up by target cells.
• In addition, scientists are investigating these extracellular miRNAs as potential biomarkers for a variety of illnesses.

b. Small interfering RNAs

• Small Interfering RNAs (siRNA) are non-coding, double-stranded RNAs that suppress gene expression via RNA interference.
• They inhibit gene expression by degrading messenger RNA and inhibiting protein translation.
• Using Dicer, large double-stranded RNAs are converted into siRNAs.
• Once siRNA is fully produced, it binds to an RNA induced silencing complex (RISC) and mRNA is cleaved by Argonaute, a catalytic RISC protein.
• Small interfering RNAs have the potential to be used as therapeutic agents due to their potency and capacity to silence genes.
• In contrast to microRNAs, siRNAs can target a specific gene, and a single siRNA guide strand can act numerous times.

c. Enhancer RNAs

• Enhancer RNAs are the third major category of regulatory RNAs.
• It is currently unknown if they represent a distinct category of RNAs of varying lengths or a distinct subset of lncRNAs.
• Enhancers, which are recognised regulatory regions in the DNA near the genes they regulate, are transcribed in any situation.
• They increase transcription of the gene(s) controlled by the enhancer from which they are transcribed.

d. Long non-coding RNAs

• Next, Xist and other long noncoding RNAs associated with X chromosomal inactivation were connected to regulation.
• Jeannie T. Lee and others demonstrated that their initially enigmatic responsibilities are the silencing of blocks of chromatin by recruitment of Polycomb complex so that messenger RNA cannot be produced from them.
• The regulation of stem cell pluripotency and cell division has been found to involve more lncRNAs, currently defined as RNAs of more than 200 base pairs that do not appear to have coding potential.

3. Transfer-messenger RNA (tmRNA)

• Present in several bacteria and plastids. tmRNA tag proteins encoded by mRNAs without stop codons for destruction, preventing the ribosome from stalling due to the absence of a stop codon.

4. Ribozymes (RNA enzymes)

• It is now known that RNAs form intricate tertiary structures and function as biological catalysts.
• These RNA enzymes are known as ribozymes, and they have many characteristics with classical enzymes, including an active site, a substrate-binding site, and a cofactor-binding site, such as a metal ion.
• RNase P, a ribonuclease responsible for the production of tRNA molecules from bigger, precursor RNAs, was one of the first ribozymes found.
• RNase P consists of both RNA and protein; however, only the RNA component is the catalyst.

5. Double-stranded RNA (dsRNA)

• As with double-stranded DNA, this kind of RNA consists of two strands joined together. dsRNA is the genetic component of several viruses.

Synthesis of RNA – How RNA is made?

• The synthesis of RNA, known as transcription, is a crucial process that is catalyzed by an enzyme called RNA polymerase. Transcription involves using a DNA template to generate a complementary RNA molecule.
• The initiation of transcription occurs when RNA polymerase binds to a specific DNA sequence called the promoter, typically located upstream of a gene. Once bound, the enzyme unwinds the DNA double helix using its helicase activity. The RNA polymerase then moves along the template strand in the 3′ to 5′ direction, synthesizing a complementary RNA molecule. Elongation of the RNA chain proceeds in the 5′ to 3′ direction.
• During transcription, the DNA sequence also determines the location where termination of RNA synthesis will occur. Different mechanisms can be involved in terminating transcription, leading to the release of the newly synthesized RNA molecule.
• After transcription, primary transcript RNAs in eukaryotes often undergo modifications by enzymes. For instance, a poly(A) tail is added to the 3′ end of the pre-mRNA, and a 5′ cap is added to the 5′ end. These modifications help protect the RNA molecule from degradation and facilitate its processing and transport.
• In addition to DNA-dependent RNA polymerases, there are also RNA-dependent RNA polymerases (RdRPs) that utilize RNA as a template for synthesizing a new RNA strand. RNA viruses, such as poliovirus, employ RdRPs to replicate their genetic material. RdRPs are also integral components of the RNA interference pathway, a regulatory mechanism observed in many organisms.
• Overall, the synthesis of RNA through transcription plays a fundamental role in gene expression and the production of various RNA molecules, including messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs). It is a tightly regulated process that contributes to the diversity and complexity of cellular functions.

What is Double-stranded RNA?

• Double-stranded RNA (dsRNA) is a type of RNA molecule that consists of two complementary strands of RNA. It resembles the double-stranded structure of DNA found in cells, but with the replacement of thymine by uracil and the addition of one oxygen atom. dsRNA can be found in various contexts, including as the genetic material of certain viruses known as double-stranded RNA viruses.
• One important aspect of dsRNA is its ability to trigger specific cellular responses in different organisms. In eukaryotes, dsRNA can initiate a process called RNA interference (RNAi). During RNAi, dsRNA molecules are recognized by cellular machinery and processed into small interfering RNAs (siRNAs). These siRNAs then guide the degradation or silencing of complementary mRNA molecules, effectively regulating gene expression. RNAi has important roles in cellular processes such as gene regulation, development, and defense against viral infections.
• In addition to its involvement in RNAi, dsRNA also plays a role in the innate immune response of vertebrates. When dsRNA is detected within a cell, it can activate an antiviral response mediated by the production of interferons. Interferons are signaling proteins that trigger a cascade of immune responses to combat viral infections and protect neighboring cells from viral spread.
• The recognition of dsRNA by the immune system is an important defense mechanism against viral infections in vertebrates. It serves as a way to detect the presence of viral genetic material and initiate a rapid antiviral response. The immune response triggered by dsRNA can lead to the activation of various defense mechanisms, including the production of antiviral proteins and the recruitment of immune cells to clear the infection.
• Overall, dsRNA plays significant roles in cellular processes and host defense mechanisms. Whether it is as the genetic material of certain viruses or as a trigger for RNA interference and immune responses, the unique structure and properties of dsRNA make it a crucial player in the regulation of gene expression and the defense against viral infections in different organisms.

What is Circular RNA?

• Circular RNA (circRNA) is a unique form of RNA that is characterized by its covalently closed, circular structure. Unlike most RNA molecules that have linear sequences, circRNAs form a continuous loop with no free ends. The discovery of circRNAs dates back to the late 1970s when it was observed that they are expressed in various organisms across the animal and plant kingdoms.
• The formation of circRNAs occurs through a process known as “back-splicing.” During back-splicing, a spliceosome, which is a complex of RNA and protein, joins a downstream 5′ donor splice site with an upstream 3′ acceptor site, creating a circular structure. This process is distinct from the canonical splicing that produces linear RNA molecules.
• The functional roles of circRNAs are still not fully understood, and ongoing research is aimed at unraveling their diverse functions. However, some studies have provided insights into the potential functions of circRNAs. One notable function is their ability to act as “microRNA sponges.” MicroRNAs are small RNA molecules that regulate gene expression by binding to messenger RNA (mRNA) and inhibiting its translation into protein. Certain circRNAs have been shown to contain binding sites for specific microRNAs, effectively sequestering them and preventing their interaction with target mRNAs. This process is referred to as microRNA sponging and suggests that circRNAs may play a role in fine-tuning gene expression by modulating the availability of microRNAs.
• Beyond their microRNA sponging activity, the functions of circRNAs are still largely unknown and an active area of research. It is likely that circRNAs have diverse roles in cellular processes and biological pathways that are yet to be fully characterized. As technology and methodologies advance, more studies are being conducted to uncover the functional significance of circRNAs in development, disease, and other biological contexts.
• In summary, circular RNA (circRNA) is a distinct form of RNA that exists as a closed loop structure. They are generated through back-splicing and have been identified in a wide range of organisms. While the exact functions of circRNAs are still being elucidated, their ability to sponge microRNAs has been demonstrated in some cases. Further research will continue to shed light on the functional significance and regulatory roles of circRNAs in cellular processes.

Functions of RNA

RNA, or ribonucleic acid, serves various important functions within cells. Here are the key functions of RNA:

• Genetic Messenger: RNA acts as a messenger between DNA and ribosomes during protein synthesis. Messenger RNA (mRNA) is synthesized in the nucleus through a process called transcription. It carries the genetic information from DNA and delivers it to the ribosomes in the cytoplasm, where proteins are synthesized based on the encoded instructions.
• Genetic Material: In some organisms, RNA serves as the genetic material itself. For example, in certain viruses, RNA carries the genetic information necessary for viral replication and protein synthesis.
• Catalytic Activity: Certain RNA molecules, known as ribozymes, possess catalytic activity. They can catalyze biological reactions, including the cutting and joining of other RNA molecules. Ribozymes can also be involved in important cellular processes such as splicing of pre-mRNA during gene expression.
• Gene Expression Control: RNA molecules play a crucial role in controlling gene expression. Small RNA molecules, such as microRNAs and small interfering RNAs, regulate gene expression by binding to complementary mRNA sequences, leading to mRNA degradation or inhibition of translation.
• Sensing and Signaling: RNA molecules can sense and respond to cellular signals. For example, long non-coding RNAs (lncRNAs) have been found to play roles in cellular processes such as development, differentiation, and response to stress signals. They can interact with other molecules and modulate gene expression and signaling pathways.
• Ribosomal Function: Ribosomal RNA (rRNA) is a major component of ribosomes, the cellular structures responsible for protein synthesis. rRNA helps in the assembly of ribosomal subunits and is involved in reading and decoding the information carried by mRNA during translation.
• Amino Acid Delivery: Transfer RNA (tRNA) molecules carry specific amino acids to the ribosomes during protein synthesis. Each tRNA molecule recognizes a specific codon on mRNA through its anticodon region and delivers the corresponding amino acid to the growing polypeptide chain.

These functions highlight the versatility of RNA in cellular processes, including information transfer, catalysis, gene regulation, and protein synthesis. RNA’s ability to carry genetic information, catalyze reactions, and participate in complex cellular processes makes it a crucial molecule for life.

FAQ

References

• https://www.ncbi.nlm.nih.gov/books/NBK558999/
• https://en.wikipedia.org/wiki/RNA
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• https://microbenotes.com/rna-properties-structure-types-and-functions/
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