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.
Reference.
Suvar
June 12, 2006 19:55
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