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The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA.

The EMBO journal | Dec 15, 2010

Star-PAP is a poly (A) polymerase (PAP) that is putatively required for 3'-end cleavage and polyadenylation of a select set of pre-messenger RNAs (mRNAs), including heme oxygenase (HO-1) mRNA. To investigate the underlying mechanism, the cleavage and polyadenylation of pre-mRNA was reconstituted with nuclear lysates. siRNA knockdown of Star-PAP abolished cleavage of HO-1, and this phenotype could be rescued by recombinant Star-PAP but not PAPα. Star-PAP directly associated with cleavage and polyadenylation specificity factor (CPSF) 160 and 73 subunits and also the targeted pre-mRNA. In vitro and in vivo Star-PAP was required for the stable association of CPSF complex to pre-mRNA and then CPSF 73 specifically cleaved the mRNA at the 3'-cleavage site. This mechanism is distinct from canonical PAPα, which is recruited to the cleavage complex by interacting with CPSF 160. The data support a model where Star-PAP binds to the RNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs.

Pubmed ID: 21102410 RIS Download

Mesh terms: Cell Extracts | Cell Line | Cleavage And Polyadenylation Specificity Factor | Gene Knockdown Techniques | Heme Oxygenase-1 | Humans | Polynucleotide Adenylyltransferase | RNA Precursors | RNA Processing, Post-Transcriptional | RNA, Small Interfering | Sensitivity and Specificity

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM051968
  • Agency: NIGMS NIH HHS, Id: R01 GM057549
  • Agency: NIGMS NIH HHS, Id: R01 GM114386
  • Agency: NIGMS NIH HHS, Id: GM057549

Gene Ontology (Data, Gene Annotation)

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