Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis
書誌事項
- 公開日
- 2020-05
- 資源種別
- journal article
- 権利情報
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- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- http://creativecommons.org/licenses/by-nc-nd/4.0/
- DOI
-
- 10.1016/j.celrep.2020.107542
- 公開者
- Elsevier BV
この論文をさがす
説明
RNA-binding proteins (RBPs) play a pivotal role in gene expression by modulating the stability of transcripts. However, the identification of degradation target mRNAs of RBPs remains difficult. By the combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to human Pumilio 1 (PUM1), we identify 48 mRNAs that both bind to PUM1 and exhibit PUM1-dependent degradation. Analysis of changes in the abundance of PUM1 and its degradation target mRNAs in RNA-seq data indicate that DNA-damaging agents negatively regulate PUM1-mediated mRNA decay. Cells exposed to cisplatin have reduced PUM1 abundance and increased PCNA and UBE2A mRNAs encoding proteins involved in DNA damage tolerance by translesion synthesis (TLS). Cells overexpressing PUM1 exhibit impaired DNA synthesis and TLS and increased sensitivity to the cytotoxic effect of cisplatin. Thus, our method identifies target mRNAs of PUM1-mediated decay and reveals that cells respond to DNA damage by inhibiting PUM1-mediated mRNA decay to activate TLS.
収録刊行物
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- Cell Reports
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Cell Reports 31 (5), 107542-, 2020-05
Elsevier BV
