論文

査読有り 国際誌
2017年8月

DDX54 regulates transcriptome dynamics during DNA damage response.

Genome research
  • Miha Milek
  • Koshi Imami
  • Neelanjan Mukherjee
  • Francesca De Bortoli
  • Ulrike Zinnall
  • Orsalia Hazapis
  • Christian Trahan
  • Marlene Oeffinger
  • Florian Heyd
  • Uwe Ohler
  • Matthias Selbach
  • Markus Landthaler
  • 全て表示

27
8
開始ページ
1344
終了ページ
1359
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1101/gr.218438.116
出版者・発行元
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT

The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of post-transcriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar proteins, showed increased binding to poly(A)+ RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well-defined class of pre-mRNAs that harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Because DDX54 promotes survival after exposure to IR, its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR.

リンク情報
DOI
https://doi.org/10.1101/gr.218438.116
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28596291
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538551
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000406354300006&DestApp=WOS_CPL
ID情報
  • DOI : 10.1101/gr.218438.116
  • ISSN : 1088-9051
  • eISSN : 1549-5469
  • PubMed ID : 28596291
  • PubMed Central 記事ID : PMC5538551
  • Web of Science ID : WOS:000406354300006

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