DNA polymerase η is regulated by poly(rC)-binding protein 1 via mRNA stability

Cong Ren, Seong Jun Cho, Yong Sam Jung, Xinbin Chen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

POLH (DNA polymerase η), a target of p53 tumour suppressor, plays a key role in TLS (translesion DNA synthesis). Loss of POLH is responsible for the human cancer-prone syndrome XPV (xeroderma pigmentosum variant). Owing to its critical role in DNA repair and genome stability, POLH expression and activity are regulated by multiple pathways. In the present study, we found that the levels of both POLH transcript and protein were decreased upon knockdown of the transcript encoding PCBP1 [poly(rC)- binding protein 1]. We also found that the half-life of POLH mRNA was markedly decreased upon knockdown of PCBP1. Moreover, we found that PCBP1 directly bound to the POLH 3'- UTR and the PCBP1-binding site in POLH mRNA is an atypical AU-rich element. Finally, we showed that the AU-rich element in POLH 3'-UTRwas responsive to PCBP1 and sufficient for PCBP1 to regulate POLH expression. Taken together, we uncovered a novel mechanism by which POLH expression is controlled by PCBP1 via mRNA stability.

Original languageEnglish (US)
Pages (from-to)377-386
Number of pages10
JournalBiochemical Journal
Volume464
DOIs
StatePublished - Dec 15 2014

Keywords

  • AU-rich element
  • DNApolymerase η (POLH)
  • MRNA decay
  • P53
  • Poly(rC)-binding protein 1 (PCBP1)
  • RNA-binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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