- RNA is a polymer of ribonucleotides composed of ribose and the bases adenine, guanine, cytosine, and uracil (instead of thymine).
- Similar to DNA, the nucleotides are connected by a phosphodiester bond.
- Most RNA molecules consist of a single strand.
- However, an RNA strand can create secondary structures such as hairpins with complementary base pairing and helical organisation by coiling back on itself.
- In many instances, the creation of double-stranded regions in RNA is crucial to its function.
- RNA is a ribonucleic acid that aids in the body’s protein synthesis. This nucleic acid is responsible for the human body’s generation of new cells.
- Typically, it is extracted from the DNA molecule.
- The main difference between RNA and DNA is that RNA contains only a single ribose sugar molecule and a single strand, as opposed to DNA, which contains two strands. Thus, the term Ribonucleic acid was coined.
- RNA is sometimes known as an enzyme since it facilitates chemical reactions in the body.
- DNA is a complicated molecule that resides predominantly in the nucleus of cells.
- All living species include DNA, which contains genetic information.
- RNA’s backbone is composed of ribose rather than the 2′-deoxyribose found in DNA. A hydroxyl group is located at the 2′ position of ribose.
- DNA is composed of the nucleotides adenine (A), guanine (G), cytosine (C), and thymine (T) (T).
- In RNA, uracil replaces thymine in DNA.
- The only structural difference between uracil and thymine is that uracil lacks a 5′ methyl group. 5′-Methyl-uracil can alternatively be written as thymine.
History of RNA
Friedrich Miescher discovered nucleic acids in 1868 and named the material nuclein since it was located in the nucleus; this led to the discovery of RNA. The most significant event in the history of RNA is listed below.
- The involvement of DNA in protein synthesis was suggested in 1939.
- Severo Ochoa was awarded the Nobel Prize in 1959 for discovering the RNA production mechanism.
- Robert W. Holley sequences 77 nucleotides of yeast tRNA in 1965.
- The sensitivity of RNA to the alkaline –OH group on ribose distinguished it from DNA.
- ATP and GTP were to serve as the primary source of energy and building blocks for RNA.
- Adenine, cytosine, and guanine were the three bases shared by RNA and DNA, although RNA has Uracil instead of thymine.
Difference between DNA and RNA
RNA is a polymer of ribonucleotides connected via 3c,5c-phosphodiester bridges. Although RNA and DNA share certain structural similarities, they have distinct distinctions.
- Pentose: The sugar in RNA is ribose as opposed to deoxyribose in DNA.
- Pyrimidine: RNA consists of uracil, a pyrimidine, in place of thymine (in DNA).
- Single strand : RNA typically consists of a single-stranded polynucleotide. If complementary base pairs are in close proximity, however, this strand may fold at specific locations to form a double-stranded structure.
- Chargaff’s rule was disregarded: There is no specific relationship between purine and pyrimidine content due to the single-stranded structure of DNA. Thus, the ratio of guanine to cytosine is not equal (as is the case in DNA).
- Susceptibility to alkali hydrolysis : Alkali can convert RNA to 2c,3c-cyclic diesters via hydrolysis. Due to the presence of a hydroxyl group at the 2c position, this is conceivable. Due to the absence of this group, alkali hydrolysis cannot be performed on DNA.
- Orcinol colour reaction : Due to the presence of ribose, RNAs can be histologically detected using the orcinol colour reaction.
Structure of RNA
- RNA’s fundamental structure consists of nucleotides connected to ribose sugars by 5′-3′ phosphodiester linkages.
- Ribose has the chemical formula C5H10O5 and occurs naturally as D-ribose and less frequently as L-ribose.
- The D and L designations correspond to the locations of the hydroxyl group.
- There are four nucleotide bases: adenine, guanine, cytosine, and uracil.
- Between adenine and uracil, two hydrogen bonds develop, while between cytosine and guanine, three bonds form.
- The pairing of bases via hydrogen bonds is the foundation of the secondary structure of RNA.
- The tertiary structure of RNA is the consequence of RNA folding, which generates a three-dimensional shape composed of helices and grooves.
- RNA is distinct from DNA in that it contains uracil instead of thymine and a 2′ hydroxyl group instead of a 2′ hydrogen.
- The 2′ hydroxyl group contributes to RNA conformation via its interaction with the solvent environment.
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)
What do you mean by Secondary Structure of RNA?
- The vast majority of RNA molecules are single-stranded, although an RNA molecule may have sections that can create complementary base pairings in locations where the RNA strand loops back on itself.
- If so, some sections of the RNA will be double-stranded.
- Ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as some messenger RNAs, have extensive secondary structure (mRNAs).
Functions of RNA
The ribonucleic acid – RNA, which is mostly constituted of nucleic acids, is found in all living species, including bacteria, viruses, plants, and animals, and is responsible for a range of cellular processes. In addition to serving as structural molecules in cell organelles, these nucleic acids catalyse metabolic events. The many forms of RNA are engaged in a variety of biological processes. The key roles of RNA are:
- Facilitate the protein synthesis from DNA
- During protein synthesis, serves as an adaptor molecule
- Acts as a liaison between the DNA and ribosomes.
- They are the genetic information carrier in all living cells.
- Encourages the ribosomes to select the needed amino acid for the synthesis of new proteins in the body.
Types of RNA
The three major types of RNAs with their respective cellular composition are given below
- Messenger RNA (mRNA) : 5–10%
- Transfer RNA (tRNA) : 10–20%
- Ribosomal RNA (rRNA) : 50–80%
Messenger RNA (mRNA)
- mRNA accounts for only 5% of total RNA in the cell. It is the most diverse of the three RNA kinds in terms of nucleotide sequence and size.
- This form of RNA acts by conveying genetic material to ribosomes and transmitting instructions regarding the protein types required by bodily cells.
- In general, eukaryotic mRNA is more stable and has a longer half-life than bacterial mRNA.
- According to their functions, various forms of RNA are known as messenger RNA. Therefore, mRNA plays an essential function in the transcription process or during protein synthesis.
- It is a complementary copy of the gene that has been transcribed from DNA and is ready to be translated into proteins. mRNA includes a codon consisting of three nucleotides (triplets) that is unique to an amino acid.
- There are 20 amino acids that are encoded by 64 unique triplets of 4 nucleotides, as a single amino acid can be encoded by many codons.
- The most common start codon is the AUG codon for methionine, which specifies the amino acid at the NH2-terminus of a protein chain. Three codons are stop codons and do not designate any amino acids.
- mRNA is detected during translation in eukaryotic post-transcriptional processing when its 5′ end is bound with guanosine triphosphate (GTP). This is referred to as capping.
Properties of mRNA
- DNA is transcribed into mRNA, which contains the blueprint for protein synthesis.
- Prokaryotic mRNA does not require processing and can proceed directly to protein synthesis.
- A freshly generated RNA transcript in eukaryotes is designated pre-mRNA and must undergo maturation to become mRNA.
- Introns and exons are the non-coding and coding sections, respectively, of pre-mRNA.
- During the processing of pre-mRNA, the introns are spliced and the exons are linked. The 5′ end of the RNA transcript is capped with 7-methylguanosine, while the 3′ end is polyadenylated.
- A poly(A) tail, which is a sequence of adenine nucleotides, is added to the transcript during the polyadenylation process.
- The 5′ cap safeguards the mRNA from destruction, while the 3′ poly(A) tail contributes to the mRNA’s stability and aids in its transport.
Function of mRNA
- mRNA converts DNA’s genetic code into a form that can be read and used to manufacture proteins. mRNA transports genetic information from a cell’s nucleus to its cytoplasm.
- rRNA is a component of the ribosome and is present in the cytoplasm of a cell, where ribosomes are located.
- The ribosomal RNA is essential for the synthesis and translation of mRNA into proteins in all living cells.
- The rRNA is constituted primarily of cellular RNA and is the most abundant RNA in the cells of all living organisms.
- It accounts for 80% of the cell’s total RNA.
- It binds amino acids into a polypeptide chain as it proceeds along an mRNA molecule.
- The binding of mRNA and individual aminoacyl-tRNA to the most abundant RNA protein complex in the cell, the ribosome, considerably increases the efficiency of translation.
- A ribosome is composed of multiple rRNA molecules and about 50 proteins organised into a large subunit (50S) and a small subunit (20S) (30S).
- Additionally, the big subunit contains one accessory RNA.
- In prokaryotic and eukaryotic cells, the lengths of rRNA molecules, the amount of protein in each subunit, and the size of subunits varies.
- rRNA generates ribosomes, which are required for protein synthesis.
Properties of rRNA
- rRNA generates ribosomes, which are required for protein synthesis.
- A ribosome has both a big and a tiny subunit.
- In prokaryotes, a 70S ribosome is composed of a tiny 30S subunit and a big 50S subunit. The 40S and 60S subunits combine to generate an 80S ribosome in eukaryotes.
- Exit (E), peptidyl (P), and acceptor (A) sites are present on ribosomes to bind aminoacyl-tRNAs and connect amino acids to form polypeptides.
Function of rRNA-Ribosomal RNA
- rRNA regulates the translation of messenger RNA into proteins.
tRNA – Transfer RNA
- The transfer RNA is accountable for selecting the correct protein or amino acids necessary by the organism, so assisting the ribosomes.
- It resides at the terminal ends of each amino acid.
- This is also known as soluble RNA, and it connects the messenger RNA to the amino acid.
- tRNA is the smallest of the three RNA kinds, with 70-80 nucleotides.
- Transferring amino acids during protein synthesis is crucial for translation, as they are required for protein synthesis. Thus tRNAs are referred to as transfer RNAs (tRNA).
- At least 20 distinct tRNAs exist, one for each amino acid with a particular binding site for each of the 20 amino acids added to the developing polypeptide chain.
- The tRNA interprets the mRNA codon using its own anticodon, and hydrogen bonds are used to couple the bases. Methylation of the bases results in the formation of additional bases that differ from the standard four.
- Methylguanine and methylcytosine are two common examples of methylated bases.
- tRNA molecules fold into a two-dimensional stem-loop configuration that resembles a cloverleaf.
- Its structure consists of an acceptor arm for the attachment of particular amino acids and a stem loop with a three-base anticodon sequence at each end.
- The anticodon can form base pairs with the mRNA codon or codons that correspond to it.
Properties of tRNA – Transfer RNA
- tRNAs are RNA molecules responsible for translating mRNA into proteins.
- They have a cloverleaf structure with a 3′ acceptor site, a 5′ terminal phosphate, a D arm, a T arm, and an anticodon arm.
- With the assistance of aminoacyl-tRNA synthetase, the major function of a tRNA is to transport amino acids to the 3′ acceptor site of a ribosome.
- Aminoacyl-tRNA synthetases are enzymes that attach the correct amino acid to a free tRNA in order to build proteins.
- Once an amino acid is attached to tRNA, it is referred to as aminoacyl-tRNA.
- The kind of amino acid on a tRNA is determined by the mRNA codon, which is a three-nucleotide sequence that encodes for an amino acid.
- The anticodon is located on the anticodon arm of the tRNA, which is complementary to an mRNA codon and specifies which amino acid to transport.
- Additionally, tRNAs regulate apoptosis by serving as cytochrome c scavengers.
Functions of tRNA – Transfer RNA
- Transfer RNA delivers or transfers amino acids to the ribosome that correspond to each codon of rRNA containing three nucleotides. The amino acids can subsequently be combined and transformed into polypeptides and proteins.
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.
- 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.
How RNA is made?
- RNA polymerases create RNA from DNA via the transcription process.
- In prokaryotes, all kinds of RNA transcription are catalysed by a single RNA polymerase.
- There are various types of RNA polymerases in eukaryotes, each of which is responsible for generating a specific RNA.
- RNA polymerase I produces rRNA. RNA polymerase II generates messenger RNA (mRNA), whereas RNA polymerase III generates transfer RNA (tRNA).
- An RNA polymerase enzyme connects to a promoter region on DNA to induce transcription, at which point the DNA double helix unwinds into a template strand and non-coding strand.
- RNA polymerase uses the 3′-5′ DNA template strand to generate a 5′-3′ RNA strand with complementary nucleotides during transcription.
- Except for the substitution of uracil for thymine, the newly produced RNA strand resembles the noncoding strand of DNA.
- Each RNA polymerase in eukaryotes has a distinct way to halt transcription.
- RNA polymerase II-transcribed RNA, for instance, contains an AAUAAA poly(A) site that recruits a collection of cleavage factors.
- Termination of prokaryotic RNA can be Rho-dependent or Rho-independent.
- Rho-dependent termination occurs when a Rho factor helicase attaches to C-rich sites on the RNA and ATP hydrolysis drives Rho to unwind the DNA-RNA complex and release the RNA transcript.
- Rho-independent termination, on the other hand, employs a hairpin loop that causes the RNA polymerase to stall and permits the release of the RNA transcript.