The structure of human Cleavage Factor Im hints at functions beyond UGUA-specific RNA binding: A role in alternative polyadenylation and a potential link to 5’ capping and splicing

 Abstract

3’-end cleavage and subsequent polyadenylation are critical steps in mRNA maturation. The precise location where cleavage occurs (referred to as poly(A) site) is determined by a tripartite mechanism in which a A(A/U)UAAA hexamer, GU rich downstream element and UGUA upstream element are recognized by the cleavage and polyadenylation factor (CPSF), cleavage stimulation factor (CstF) and cleavage factor Im (CFIm), respectively. CFIm is composed of a smaller 25 kDa subunit (CFIm25) and a larger 59, 68 or 72 kDa subunit. CFIm68 interacts with CFIm25 through its N-terminal RNA recognition motif (RRM). We recently solved the crystal structures of CFIm25 bound to RNA and of a complex of CFIm25, the RRM domain of CFIm68 and RNA. Our study illustrated the molecular basis for UGUA recognition by the CFIm complex, suggested a possible mechanism for CFIm mediated alternative polyadenylation, and revealed potential links between CFIm and other mRNA processing factors, such as the 20 kDa subunit of the cap binding protein (CBP20), and the splicing regulator U2AF65.

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748 - 753
doi
10.4161/rna.8.5.16040
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The structure of human Cleavage Factor Im hints at functions beyond UGUA-specific RNA binding: A role in alternative polyadenylation and a potential link to 5’ capping and splicing