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Mammalian mRNA Polyadenylation Machinery

Mammalian mRNA Polyadenylation Machinery.

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Mammalian mRNA Polyadenylation Machinery

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  1. Mammalian mRNA Polyadenylation Machinery

  2. Cleavage-and-polyadenylation specificity factor (CPSF) binds via recognition of AAUAAA polyadenylation signals. CPSF consists of proteins of 160, 100, 73 and 30 kDa. The 160 kDa and 30 kDa proteins appear to be involved in sequence recognition. Then Cleavage stimulation factor (CstF) binds to a downstream G/U element. CstF consists of proteins of 77, 64 and 50 kDa. The 64 kDa protein appears to have the sequence recognition and RNP binding domain. CPSF and CstF interact across a cleavage site, stabilize each other and direct the subsequent binding of cleavage factors, CFI and CFII, to the cleavage site (arrow), followed by poly(A) polymerase (PAP). The CTD (C-Terminal Domain) of RNA Pol II is thought to strongly stimulate the 3’ cleavage reaction, which requires ATP, but ATP hydrolysis is not necessary. Slow polyadenylation occurs followed by release of CFI and CFII and CstF. The released 3' end of pre-mRNA is rapidly degraded. Poly(A)-binding protein II (PABII) binds to the growing poly(A) tail (further details see slide “RNA Polyadenylation). Adapted from Shatkin A.J. et al, Nature Structural Biology 7:838, 2000 and Barnard D.C. et al, Cell 119:641, 2004. Mammalian mRNA Polyadenylation Machinery

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