Полиаденилирование
мРНК гистоновых генов и ряда других не полиаденилируется. Полиаденилированные про-mРНК подвергаются сплайсингу. После синтеза про-mРНК на расстоянии примерно 20 н в направлении 3'-конца от последовательности 5'-AAУAA-3' происходит разрезание эндонуклеазой и к новому 3'-концу присоединяется от 30 до 300 остатков АМФ (безматричный синтез). ПолиА хвост защищает 3'-конец от гидролиза, т.к. покрыт полиА-связывающими белками. Время жизни mРНК зависит от длинны полиА-хвоста.
Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA (mRNA) molecule. It is part of the route to producing mature messenger RNA for translation, in the larger process of protein synthesis to produce proteins. In eukaryotic organisms, polyadenylation is the mechanism by which most messenger RNA molecules are terminated at their 3' ends. The polyadenosine (poly-A) tail protects the mRNA molecule from exonucleases and is important for transcription termination, for export of the mRNA from the nucleus, and for translation. Some prokaryotic mRNAs also are polyadenylated, although the polyadenosine tail's function is different from that in eukaryotes.
Polyadenylation occurs during and immediately after transcription of DNA into RNA in the nucleus. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. The cleavage site is characterized by the presence of the base sequence AAUAAA near the cleavage site. After the mRNA has been cleaved, 50 to 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase.
Polyadenylation Process
The Process of PolyadenylationCleavage and Polyadenylation Specificity Factor (CPSF) and Cleavage Stimulation Factor (CstF), both of which are multi-protein complexes, start bound to the rear of the advancing RNA polymerase II.
As the RNA polymerase II advances over the adenylation signal sequences CPSF and CstF transfer to the new pre-mRNA, CPSF binding to the AAUAAA sequence, and CstF to the GU or U rich sequence following it.
CPSF and CstF promote cleavage approximately 35 nucleotides after the end of the AAUAAA sequence. Immediately Polyadenylate Polymerase (PAP) starts writing the polyadenosine tail. Polyadenosine Binding (PAB) protein immediately binds to the new polyadenosine sequence.
CPSF dissociates, and polyadenylation by PAP continues to write an adenosine tail of approximately 50 to 250 nucleotides, depending on the organism. PAB acts as some kind of molecular ruler, specifying when polyadenylation should stop.
PAP dissociates, and PAB remains bound. Along whith the 5' cap it is thought this helps target the mRNA for nuclear export.
Polyadenylation is initially dependent on CPSF and the AAUAAA sequence (for the first 10 As or so), after which polyadenylation is simply dependent on the existing poly A tail.