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- W2894420996 abstract "Cleavage and polyadenylation (C/P) of mRNA is an important cellular process that promotes increased diversity of mRNA isoforms and could change their stability in different cell types. The cleavage stimulation factor (CstF) complex, part of the C/P machinery, binds to U- and GU-rich sequences located downstream from the cleavage site through its RNA-binding subunit, CstF-64. Less is known about the function of the other two subunits of CstF, CstF-77 and CstF-50. Here, we show that the carboxy-terminus of CstF-77 plays a previously unrecognized role in enhancing C/P by altering how the RNA recognition motif (RRM) of CstF-64 binds RNA. In support of this finding, we also show that CstF-64 relies on CstF-77 to be transported to the nucleus; excess CstF-64 localizes to the cytoplasm, possibly via interaction with cytoplasmic RNAs. Reverse genetics and nuclear magnetic resonance studies of recombinant CstF-64 (RRM-Hinge) and CstF-77 (monkeytail-carboxy-terminal domain) indicate that the last 30 amino acids of CstF-77 increases the stability of the RRM, thus altering the affinity of the complex for RNA. These results provide new insights into the mechanism by which CstF regulates the location of the RNA cleavage site during C/P." @default.
- W2894420996 created "2018-10-05" @default.
- W2894420996 creator A5020647459 @default.
- W2894420996 creator A5062624248 @default.
- W2894420996 creator A5068683652 @default.
- W2894420996 creator A5090774479 @default.
- W2894420996 date "2018-09-26" @default.
- W2894420996 modified "2023-09-26" @default.
- W2894420996 title "The structural basis of CstF-77 modulation of cleavage and polyadenylation through stimulation of CstF-64 activity" @default.
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- W2894420996 doi "https://doi.org/10.1093/nar/gky862" @default.
- W2894420996 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6294498" @default.
- W2894420996 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30257008" @default.
- W2894420996 hasPublicationYear "2018" @default.
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