LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation

EMBO J. 2020 Feb 3;39(3):e102729. doi: 10.15252/embj.2019102729. Epub 2019 Nov 29.

Abstract

A number of long noncoding RNAs (lncRNAs) are induced in response to specific stresses to construct membrane-less nuclear bodies; however, their function remains poorly understood. Here, we report the role of nuclear stress bodies (nSBs) formed on highly repetitive satellite III (HSATIII) lncRNAs derived from primate-specific satellite III repeats upon thermal stress exposure. A transcriptomic analysis revealed that depletion of HSATIII lncRNAs, resulting in elimination of nSBs, promoted splicing of 533 retained introns during thermal stress recovery. A HSATIII-Comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) analysis identified multiple splicing factors in nSBs, including serine and arginine-rich pre-mRNA splicing factors (SRSFs), the phosphorylation states of which affect splicing patterns. SRSFs are rapidly de-phosphorylated upon thermal stress exposure. During stress recovery, CDC like kinase 1 (CLK1) was recruited to nSBs and accelerated the re-phosphorylation of SRSF9, thereby promoting target intron retention. Our findings suggest that HSATIII-dependent nSBs serve as a conditional platform for phosphorylation of SRSFs by CLK1 to promote the rapid adaptation of gene expression through intron retention following thermal stress exposure.

Keywords: intron retention; noncoding RNA; nuclear stress bodies; phosphorylation; splicing factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Nucleus / metabolism*
  • Cricetulus
  • Exome Sequencing
  • Gene Expression Profiling
  • Gene Expression Regulation
  • HeLa Cells
  • Heat-Shock Response*
  • Humans
  • Introns
  • Microsatellite Repeats*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism*
  • RNA Splicing Factors / metabolism
  • RNA, Long Noncoding / metabolism*
  • Serine-Arginine Splicing Factors / metabolism*

Substances

  • RNA Splicing Factors
  • RNA, Long Noncoding
  • SRSF9 protein, human
  • Serine-Arginine Splicing Factors
  • Clk dual-specificity kinases
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases