2017年8月
DDX54 regulates transcriptome dynamics during DNA damage response.
Genome research
- 巻
- 27
- 号
- 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