Heterogeneous Nuclear Ribonucleoprotein G Regulates Splice Site Selection by Binding to CC(A/C)-rich Regions in pre-mRNA

J Biol Chem. 2009 May 22;284(21):14303-15. doi: 10.1074/jbc.M901026200. Epub 2009 Mar 12.

Abstract

Almost every protein-coding gene undergoes pre-mRNA splicing, and the majority of these pre-mRNAs are alternatively spliced. Alternative exon usage is regulated by the transient formation of protein complexes on the pre-mRNA that typically contain heterogeneous nuclear ribonucleoproteins (hnRNPs). Here we characterize hnRNP G, a member of the hnRNP class of proteins. We show that hnRNP G is a nuclear protein that is expressed in different concentrations in various tissues and that interacts with other splicing regulatory proteins. hnRNP G is part of the supraspliceosome, where it regulates alternative splice site selection in a concentration-dependent manner. Its action on alternative exons can occur without a functional RNA-recognition motif by binding to other splicing regulatory proteins. The RNA-recognition motif of hnRNP G binds to a loose consensus sequence containing a CC(A/C) motif, and hnRNP G preferentially regulates alternative exons where this motif is clustered in close proximity. The X-chromosomally encoded hnRNP G regulates different RNAs than its Y-chromosomal paralogue RNA-binding motif protein, Y-linked (RBMY), suggesting that differences in alternative splicing, evoked by the sex-specific expression of hnRNP G and RBMY, could contribute to molecular sex differences in mammals.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism
  • Exons / genetics
  • Genes, Reporter
  • Heterogeneous-Nuclear Ribonucleoproteins / chemistry
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • RNA Precursors / genetics*
  • RNA Splice Sites / genetics*
  • RNA Splicing / genetics
  • Rats
  • Spliceosomes / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nuclear Proteins
  • RBMX protein, rat
  • RNA Precursors
  • RNA Splice Sites