Five prime cap

The cap structure (in German cap ) is a chemical modification of mRNA molecules in eukaryotes, which increases the stability of the RNA dramatically important for the transport of the RNA out of the nucleus into the cytoplasm, and the translation of mRNAs by subsequent ribosome is.

It usually is a modified guanine nucleotide that is linked via a 5'- 5 ' phosphodiester rare at the head end of the RNA during transcription of the gene (English capping ). The reaction starts already after a few nucleotides of the mRNA were attached by the RNA polymerase. Capping can thus be considered as cotranskriptionell, even though it could very well take place after transcription, in principle. In contrast, the splicing and polyadenylation (English tailing ) are post-transcriptional processes that start after drop of the mRNA by the RNA polymerase.

Capping is except for mRNA also found in many non-coding RNAs.

Cap structures

Polymerase II

For mRNAs that are transcribed by RNA polymerase II, there is the classic m7G cap. Here is transmitted (after hydrolysis of the terminal - phosphate by γ triphosphatase ) by the so-called capping enzyme is a GMP - rest ( GTP ) in the form of a 5'- 5 ' phosphodiester bond to the 5'- end of the RNA, and then at position 7 of the guanine using the mRNA cap- methyltransferase with the consumption of S-adenosylmethionine ( SAM), a universal methyl group donor, methylated, it results: 5'- 5 ' m7GpppN. In addition, there are further methylation of the first bases of the mRNA at position 2 'which is then called Cap1 (only the first base methylated) or Cap2 (the first two bases methylated).

Furthermore, one finds, for example, in trypanosomes far more complex cap structures in which not only the first nucleotide is modified, but also subsequent (eg Trypanosoma brucei cap 4).

Polymerase III

Transcripts of RNA polymerase III to receive these 5 'cap structures, a few RNA is but a monomethylation of a γ - phosphate group (for example, the U6 snRNA ).

Viruses

Some viruses show a peculiarity in the biosynthetic pathway of the cap structure: GTP is first methylated and only then transferred to the RNA.

Function

As well as the poly -A tail at the 3 ' end of mRNAs, the cap structure plays an important role in stabilizing the mRNA. Without this structure, the mRNAs are rapidly degraded in the cytoplasm, from 5 'to 3' by exonucleases.

Even when discharging of the RNA out of the nucleus through the nuclear pore to the cytoplasm (RNA export) the cap has an important role. It is still bound during transcription from the cap-binding complex with other factors ensures effective transport in interaction.

The cap is of critical importance also in the initiation of translation. Both bound by CBC ( during the first round of translation ) and by eIF4E ( while all other rounds), it ensures that the ribosome is recruited and starts initialization. This leads to a ring closure of the RNA (closed loop model of translation), in which the 5'-end interacts with the poly -A tail (via eIF4E, eIF4G and the cytoplasmic poly-A binding protein PABPC ).

Because some viruses replicate exclusively in the cytoplasm, they receive from the cellular machinery no cap structure. To compensate for the disadvantages that this entails, they steal a cap of cellular mRNAs, it is called cap - snatching. An mRNA of the host organism is doing near the 5 ' end split ( which yes the cap bears ) and a so-called capped- leader to use to initiate the viral translation.

The fact that viral polymerases produce no m7G cap, to permit a specific distinction between " foreign" and " endogenous " RNA - RNA, which carries only a ungecaptes triphosphate at the 5'- end, can be considered as an indication of an infection. In fact, there are in the innate immune system (whose basic task of the distinction between " foreign " and "self " is ) with RIG- I is an intracellular receptor, precisely recognizes this structure as PAMP and subsequently triggers an antiviral immune response.