Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis
Summary: 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...
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doaj-4b519f4df52943fda03af74d378c6bde2020-11-25T03:27:01ZengElsevierCell Reports2211-12472020-05-01315Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion SynthesisToshimichi Yamada0Naoto Imamachi1Katsutoshi Imamura2Kenzui Taniue3Takeshi Kawamura4Yutaka Suzuki5Masami Nagahama6Nobuyoshi Akimitsu7Meiji Pharmaceutical University, Kiyose-shi, Tokyo 204-8588, JapanIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa-shi, Chiba 277-8562, JapanMeiji Pharmaceutical University, Kiyose-shi, Tokyo 204-8588, JapanIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720304423RNA-binding proteinsPumilioRNA stabilityRNA-seqRIP-seqBRIC-seq |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Toshimichi Yamada Naoto Imamachi Katsutoshi Imamura Kenzui Taniue Takeshi Kawamura Yutaka Suzuki Masami Nagahama Nobuyoshi Akimitsu |
spellingShingle |
Toshimichi Yamada Naoto Imamachi Katsutoshi Imamura Kenzui Taniue Takeshi Kawamura Yutaka Suzuki Masami Nagahama Nobuyoshi Akimitsu Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis Cell Reports RNA-binding proteins Pumilio RNA stability RNA-seq RIP-seq BRIC-seq |
author_facet |
Toshimichi Yamada Naoto Imamachi Katsutoshi Imamura Kenzui Taniue Takeshi Kawamura Yutaka Suzuki Masami Nagahama Nobuyoshi Akimitsu |
author_sort |
Toshimichi Yamada |
title |
Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis |
title_short |
Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis |
title_full |
Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis |
title_fullStr |
Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis |
title_full_unstemmed |
Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis |
title_sort |
systematic analysis of targets of pumilio-mediated mrna decay reveals that pum1 repression by dna damage activates translesion synthesis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-05-01 |
description |
Summary: 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. |
topic |
RNA-binding proteins Pumilio RNA stability RNA-seq RIP-seq BRIC-seq |
url |
http://www.sciencedirect.com/science/article/pii/S2211124720304423 |
work_keys_str_mv |
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