Rbm10 regulates inflammation development via alternative splicing of Dnmt3b

Toru Atsumi, Hironao Suzuki, Jing Jing Jiang, Yuko Okuyama, Ikuma Nakagawa, Mitsutoshi Ota, Yuki Tanaka, Takuto Ohki, Kokichi Katsunuma, Koichi Nakajima, Yoshinori Hasegawa, Osamu Ohara, Hideki Ogura, Yasunobu Arima, Daisuke Kamimura, Masaaki Murakami

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

RNA-binding motif 10 (Rbm10) is an RNA-binding protein that regulates alternative splicing, but its role in inflammation is not well defined. Here, we show that Rbm10 controls appropriate splicing of DNA (cytosine-5)-methyltransferase 3b (Dnmt3b), a DNA methyltransferase, to regulate the activity of NF-κB-responsive promoters and consequently inflammation development. Rbm10 deficiency suppressed NF-κB-mediated responses in vivo and in vitro. Mechanistic analysis showed that Rbm10 deficiency decreased promoter recruitment of NF-κB, with increased DNA methylation of the promoter regions in NF-κB-responsive genes. Consistently, Rbm10 deficiency increased the expression level of Dnmt3b2, which has enzyme activity, while it decreased the splicing isoform Dnmt3b3, which does not. These two isoforms associated with NF-κB efficiently, and overexpression of enzymatically active Dnmt3b2 suppressed the expression of NF-κB targets, indicating that Rbm10-mediated Dnmt3b2 regulation is important for the induction of NF-κB-mediated transcription. Therefore, Rbm10-dependent Dnmt3b regulation is a possible therapeutic target for various inflammatory diseases.

Original languageEnglish
Pages (from-to)581-591
Number of pages11
JournalInternational immunology
Volume29
Issue number12
DOIs
Publication statusPublished - 2017 Dec 1
Externally publishedYes

Keywords

  • Chemokines
  • Cytokines
  • NF-κB
  • RNA splicing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Rbm10 regulates inflammation development via alternative splicing of Dnmt3b'. Together they form a unique fingerprint.

Cite this