PCBP1 and PCBP2 both bind heavily oxidized RNA but cause opposing outcomes, suppressing or increasing apoptosis under oxidative conditions

Takashi Ishii, Tatsuhiro Igawa, Hiroshi Hayakawa, Tsugumi Fujita, Mutsuo Sekiguchi, Yusaku Nakabeppu

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

PCBP1, a member of the poly(C)-binding protein (PCBP) family, has the capability of binding heavily oxidized RNA and therefore participates in the cellular response to oxidative conditions, helping to induce apoptosis. There are four other members of this family, PCBP2, PCBP3, PCBP4, and hnRNPK, but it is not known whether they play similar roles. To learn more, we first tested their affinity for an RNA strand carrying two 8-oxo-guanine (8-oxoG) residues at sites located in close proximity to each other, representative of a heavily oxidized strand or RNA with one 8-oxoG or none. Among them, only PCBP2 exhibited highly selective binding to RNA carrying two 8-oxoG residues similar to that observed with PCBP1. In contrast, PCBP3, PCBP4, and hnRNPK bound RNA with or without 8-oxoG modifications and exhibited slightly increased binding to the former. Mutations in conserved RNA-binding domains of PCBP2 disrupted the specific interaction with heavily oxidized RNA. We next tested PCBP2 activity in cells. Compared with WT HeLa S3 cells, PCBP2-KO cells established by gene editing exhibited increased apoptosis with increased caspase-3 activity and PARP1 cleavage under oxidative conditions, which were suppressed by the expression of WT PCBP2 but not one of the mutants lacking binding activity. In contrast, PCBP1-KO cells exhibited reduced apoptosis with much less caspase-3 activity and PARP cleavage than WT cells. Our results indicate that PCBP2 as well as PCBP1 bind heavily oxidized RNA; however, the former may counteract PCBP1 to suppress apoptosis under oxidative conditions.

本文言語英語
ページ(範囲)12247-12261
ページ数15
ジャーナルJournal of Biological Chemistry
295
34
DOI
出版ステータス出版済み - 8 21 2020

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学

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