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

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 PAPĪ±. 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 PAPĪ±, 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


  • Laishram RS
  • Anderson RA


The EMBO journal

Publication Data

December 15, 2010

Associated Grants

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

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