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The 5' cap is a specially altered dinucleotide end to the 5' end of preliminary messenger RNA as found in eukaryotes. The process of 5' capping is vital to creating mature messenger RNA which is then able to undergo translation. Capping ensures the messenger RNA's stability while it undergoes translation in the process of protein synthesis, and is a highly regulated process which occurs in the nucleus.
5' Cap Structure
The 5' cap is found on the 5' end of an mRNA molecule and consists of a guanosine nucleotide connected to the mRNA via an unusual 5' to 5' triphosphate linkage.
Further modifications include the methylation of the guanosine, and the possible methylation of the 2' hydroxy-groups of the first 3 ribose sugars of the 5' end of the mRNA. The methylation of both 2' hydroxy-groups is shown on the diagram.
Functionally the 5' cap looks like the 3' end of an RNA molecule (the 5' carbon of the cap ribose is bonded, and the 3' unbonded). This provides significant resistance to 5' exonucleases.
Capping process
The starting point is the unaltered 5' end of an RNA molecule. This features a final nucleotide followed by three phosphate groups attached to the 5' carbon.
- One of the terminal phosphate groups is removed (by a phosphatase), leaving two terminal phosphates.
- GTP is added to the terminal phosphates (by a guanylyl transferase), losing two phosphate groups (from the GTP) in the process. This results in the 5' to 5' triphosophate linkage.
- The guanosine is methylated (by a methyl transferase).
- Other methyltransferases are optionally used to carry out methylation of 5' proximal nucleotoides.
5' capping targeting
The required enzymes for capping are found bound to the RNA polymerase II before transcription starts. As soon as the 5' end of the new transcript emerges the enzymes transfer to it and begin the capping process (this is a similar kind of mechanism to ensure capping as for polyadenylation).
The enzymes for capping can only bind to RNA polymerase II ensuring specificity to only these transcripts, which are almost entirely mRNA.
5' cap function
The 5' cap has 4 main functions:
- Regulation of nuclear export.
- Prevention of degradation by exonucleases.
- Promotion of translation (see ribosome and translation).
- Promotion of 5' proximal intron excision.
Nuclear export of RNA is regulated by the Cap Binding Complex (CBC) which binds exclusively to capped RNA. The CBC is then recognised by the nuclear pore complex and exported.
Degradation of the mRNA by 5' exonucleases is prevented (as mentioned above) by functionally looking like a 3' end. This increases the half life of the mRNA, essential in eukaryotes as the export process takes significant time.
The cap promotes translation, and is required for binding of ribosomes and translation initiation factors (specifically eIF-4G and eIF-4E). The CBC is also involved in this process, recruiting the initiation factors.
The mechanism of 5' proximal intron excision promotion is not well understood, but the 5' cap appears to loop round and interact with the spliceosome in the splicing process, promoting intron excision.
See also
| Post Transcriptional Modification |
|---|
| Transcription | Post transcriptional modification | RNA splicing | Polyadenylation | 5' cap |
"5' cap"