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Polyadenylation is the covalent linkage of a poly(A) tail 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, most messenger RNA molecules end with a poly-A stretch at their 3' ends. The polyadenine (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 polyadenine tail's function is different from that in eukaryotes.
Polyadenylation occurs after transcription of DNA into RNA in the nucleus. After the polyadenylation signal has been transcribed, 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 adenine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by polyadenylate polymerase.
- Cleavage 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 polyadenine tail. Cleavage will not occur unless PAP is bound to the complex, eliminating the possibility of premature cleavage. Nuclear Polyadenylate Binding Protein (PABPN1) immediately binds to the new polyadenine sequence.
- CPSF dissociates, and polyadenylation by PAP continues to write an adenine tail of approximately 100 to 250 nucleotides, depending on the organism. PABPN1 acts as some kind of molecular ruler, specifying when polyadenylation should stop. Occasionally, polyadenylation is a result of polymerase stuttering.
- PAP dissociates, and PABPN1 remains bound. It is thought this, along with the 5' cap, 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.
- Bruce Alberts et al, (February 28, 2002). Molecular Biology of the Cell (fourth edition. ISBN 0-8153-3218-1).
Related proteins and complexes: