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Divya T., Kandala and Nimmy , Mohan and Vivekanand , A and Sudheesh, AP and Reshmi , G and Rakesh S. , Laishram (2016) CstF-64 and 3�-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAP�. Nucleic acids research, 44 (2). pp. 811-23. ISSN 1362-4962

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Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation.

Item Type: Article
Subjects: Cancer Research
Depositing User: Central Library RGCB
Date Deposited: 24 Mar 2017 07:03
Last Modified: 24 Mar 2017 07:04
URI: http://rgcb.sciencecentral.in/id/eprint/319

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