RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins

Cell Rep. 2018 Oct 16;25(3):726-736.e7. doi: 10.1016/j.celrep.2018.09.041.

Abstract

RNA splicing entails the coordinated interaction of more than 150 proteins in the spliceosome, one of the most complex of the cell's molecular machines. We previously discovered that the RNA-binding motif protein 17 (RBM17), a component of the spliceosome, is essential for survival and cell maintenance. Here, we find that it interacts with the spliceosomal factors U2SURP and CHERP and that they reciprocally regulate each other's stability, both in mouse and in human cells. Individual knockdown of each of the three proteins induces overlapping changes in splicing and gene expression of transcripts enriched for RNA-processing factors. Our results elucidate the function of RBM17, U2SURP, and CHERP and link the activity of the spliceosome to the regulation of downstream RNA-binding proteins. These data support the hypothesis that, beyond driving constitutive splicing, spliceosomal factors can regulate alternative splicing of specific targets.

Keywords: CHERP; RBM17; RNA homeostasis; U2SURP; cryptic splicing; spliceosome; splicing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation*
  • HEK293 Cells
  • Humans
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / physiology*
  • RNA Splicing Factors / antagonists & inhibitors
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism*
  • RNA Splicing Factors / physiology
  • RNA Splicing*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Spliceosomes

Substances

  • CHERP protein, human
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RBM17 protein, human
  • RBM17 protein, mouse
  • RNA Splicing Factors
  • RNA-Binding Proteins