RNAs, Structure and Function
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edit RNA structure
Ribonucleic acid or RNA is a biopolymer macromolecule along with DNA. It consists of small subunits called nucleotides which are composed by:
- Purine [Adenine−(A), Guanine−(G)] or pyrimidine [Cytosine−(C), Uracil−(U)] nucleobase,
- D-ribose pentose sugar and
- Phosphate group
The nucleobase is attached on the D−ribose by an N−glycosidic bond; the ribose is bonded on the phosphate group through ester bonds and the backbone bonding between phosphate group and an adjacent ribose sugar through phosphodiester bonds. A phosphate group is attached to the 3'−carbon position of one ribose and on the 5'−carbon position of the next. RNA is relatively unstable in comparison with the DNA molecule as it contains a 2'−OH hydroxyl group that acts as a nucleophil enhancing the cleavage of the phosphodiester bond between adjacent nucleotides.
edit RNA—DNA differences
RNA and DNA are very similar in structure but they differ in 4 major points:
- DNA nucleotides include Adenine, Guanine, Thymine or Cytosine whereas RNA nucleotides instead of Thymine they involve Uracil.
- DNA is always in a double helix conformation with the 2 strands always running in anti parallel orientation whereas RNA usually exists as a single strand but it has the ability to form a double strand structure too.
- DNA has a 2'−deoxy−D−ribose pentose sugar whereas RNA has a D−ribose.
- DNA has equal portions of Adenine−Thymine and Guanine−Cytosine nucleobases as it exists as a double stranded molecule where as RNA does not as it usually exists in a single stranded form
| DNA | RNA |
| A,G,C or T nucleobase | A,G,C or U nucleobase |
| Double stranded conformation | Single and double stranded conformation |
| 2'−deoxy−D−ribose pentose sugar | D−ribose pentose sugar |
| Adenine=Thymine and Guanine=Cytosine | Adenine≠Uracil , Guanine≠Cytosine |
edit Types of RNA
RNA in contrast to DNA does not self replicate in order to proliferate but it is encoded by DNA genes. The different types of RNA are synthesized so that translation of the DNA into products is achievable. In other words with no RNA no product synthesis can occur, so DNA is useless without its RNA genes. RNA genes of DNA encode for 3 major types of RNA:
- ribosomal RNA,
- messenger RNA and
- transfer RNA
edit Ribosomal RNA - rRNA
Ribosomes are non membranous organelles that participate in the translation of mRNA into a protein product. The ribosome structure is composed of 2 subunits. A small and a large subunit each of which primarily consists of rRNA of various size and a small quantity of proteins. rRNA constitutes about the 80% of the whole RNA present in an eukaryotic cell. The large subunit consists of rRNA of 5S, 5.8S and 28S sizes whereas the small subunit consists of rRNA of 18S size. (where the S is the unit for rRNA size). These rRNAs are synthesized by transcription of the rRNA genes. However, the rRNA genes encode for all rRNAs apart from the 5S rRNA which is synthesized by the tRNA genes along with all nuclear tRNAs. RNA polymerase type I is responsible for the transcription of rRNA genes by binding on the core element−CE, which overlaps the Transcription Start Site−TSS, along with the Transcription Factors inducing the so called Transcription Initiation Complex designated as TIC. The rate of the transcription is controlled by an Upstream Control Sequence−UCS located 100 base pairs upstream to the TSS. The transcription process begins and the genes are transcribed into pre−rRNA in the following order as situated on the gene: -18S - 5.8S - 28S-. The transcription comes to an end when the Transcription Complex reaches an area rich in Adenines found at about 600 base pairs downstream of the gene, indicating its end. The pre−rRNA formed includes all rRNAs on a single strand so that cleavage has to be performed so that different size rRNAs are separated. This task is untertaken by RNases that cleave the rRNA giving rise to the differential size rRNAs.
edit Messenger RNA−mRNA
mRNA genes are the genes that encode only for proteins but this encoding has an RNA intermediate. The DNA is firstly transcribed into mRNA and subsequently translated into a protein product. So the mRNA genes are the genes that encode for mRNA in order to synthesize proteins. mRNA constitutes only the 5% of the total RNA. RNA polymerase II is the enzyme responsible for the transcription of the corresponding genes into mRNA. The polymerase binds on the TATA box which acts more or less as a promoter, located about 25 base pairs upstream the Transcription Start Site−TSS, along with the transcription factors giving rise to the Transcription Initiation Complex−TIC. In order for this complex to be functional a proper sequence of events of binding the TF and the polymerase on the promoter must occur as: TFII-D, TFII-A, TFII-B, RNA pol II, TFII-F, TFII-H TFII-E TFII-J. As soon as the TIC is formed then transcription begins giving rise to pre−mRNA which include both exons and introns. Transcription ends without recognition of an adenine rich area but rather by automatic disassembling οf the Transcription Complex. The pre−mRNA is then submitted to processing that involves splicing - removal of introns and merging of the adjacent exons- and capping - addition of 7−methylguanosine on the 5' end of the mRNA so that mRNA cannot be cleaved by exonucleases. It also serves as a recognition site of the mRNA prior to translation for the small ribosomal subunit.
edit Transfer RNA−tRNA
Transfer RNA is encoded by genes that also encode for the 5S size rRNA. RNA polymerase III is responsible for the transcription of these genes by binding on the promoter, situated about 100 base pairs downstream the Transcription Start Site -TSS, along with the Transcription Factors giving rise to the Transcription Initiation Complex. As soon as this complex is formed transcription process can begin and when the Transcription Complex faces an Adenine rich region transcription comes to an end as this area is an indication for the gene end. tRNA constitutes 15% of the total RNA and is directly involved in the translation of the mRNA. More specificaly tRNA binds onto a specific amino acid and brings it along the translation site so that it is bound on the newly synthesized peptide.
- tRNA binds to its specific amino acid recognized by its side R chain in presence of the aminoacyl tRNA synthetase enzyme. The synthetase binds the 5'-CCA-OH-3' acceptor arm with the —COOH group of the amino acid.
- When the small ribosomal subunit faces an AUG codon on the mRNA it indicates the commencing of the peptide formation. As soon as the AUG codon is recognized then the first tRNA binds on the small ribosomal subunit and on the mRNA through its anticodon arm, giving rise to the Translation Initiation Complex designated as tRNAimet. Eventually the large ribosomal subunit binds on the complex indicating the initiation of the translation process. Translation always begins with the methionine amino acid on the newly synthesized peptide.
- After translocation of the Translation complex the tRNAimet enter the Peptidyl site of the complex leaving the Aminoacyl site vacant for the next tRNA to enter, bringing together the two adjacent amino acids so that a peptide bond can be formed in presence of the peptidyl transferase enzyme. As soon as the peptide bond is formed, the tRNA is released from its amino acid in presence of the tRNA deacylase.
edit Other types of RNA
- siRNA - Small interfering RNA: Known as short interfering RNA which is a class of double stranded RNA molecules involved in the RNA interference − RNAi pathway, where it interferes with the expression of a specific genes controlling the stability of the mRNA so that, when necessary, it is disintegrated avoiding its overexpression with a consequent overproduction of proteins.
- snRNA - Small nuclear ribonucleic acid: They are RNA molecules transcribed by either RNA polymerase II along with mRNA or by RNA polymerase III along with all nuclear tRNAs and the 5S rRNA. They are primarily involved in mRNA processing such as splicing by removal of introns from pre−mRNA and also in maintenance of the telomeres. They are always associated with proteins giving rise to complexes are referred to as small nuclear ribonucleoproteins−snRNP directly associated with the splicing process.
- hnRNA - Heterogeneous nuclear ribonucleic acid: hnRNA is an immature single strand of mRNA. The terms hnRNA and pre−mRNA are almost identical.