hnRNPH1-MTR4 complex-mediated regulation of NEAT1v2 stability is critical for IL8 expression

RNA Biol. 2021 Oct 15;18(sup1):537-547. doi: 10.1080/15476286.2021.1971439. Epub 2021 Sep 1.

Abstract

Many long noncoding RNAs (lncRNAs) are localized in the nucleus and play important roles in various biological processes, including cell proliferation, differentiation and antiviral response. Yet, it remains unclear how some nuclear lncRNAs are turned over. Here we show that the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) controls expression levels of NEAT1v2, a lncRNA involved in the formation of nuclear paraspeckles. hnRNPH1 associates, in an RNA-independent manner, with the RNA helicase MTR4/MTREX, an essential co-factor of the nuclear ribonucleolytic RNA exosome. hnRNPH1 localizes in nuclear speckles and depletion of hnRNPH1 enhances NEAT1v2-mediated expression of the IL8 mRNA, encoding a cytokine involved in the innate immune response. Taken together, our results indicate that the hnRNPH1-MTR4 linkage regulates IL8 expression through the degradation of NEAT1v2 RNA.

Keywords: IL8; MTR4; NEAT1; RNA decay; hnRNPH1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Protein Binding
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Stability*
  • RNA, Long Noncoding / chemistry*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism

Substances

  • CXCL8 protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Interleukin-8
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • MTREX protein, human
  • RNA Helicases

Grants and funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Numbers: 17KK0163, 18H02570, 18KT0016, 20H03655, 20H04838, 21H04792, 21H02758 and 21K19402). N.A was supported by the Uehara Memorial Foundation and the Novartis foundation. K.T. and N.A. were supported by the Takeda Science Foundation. K.T. was supported by the Kobayashi Foundation;KAKENHI [17KK0163, 18H02570, 18KT0016, 20H03655, 20H04838, 21H04792, 21H02758 and 21K19402];