Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regionsin pre-mRNA

Bettina Heinrich, Zhaiyi Zhang, Oleg Raitskin, Michael Hiller, Natalya Benderska, Annette M. Hartmann, Laurent Bracco, David Elliott, Shani Ben-Ari, Hermona Soreq, Joseph Sperling, Ruth Sperling, Stefan Stamm

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish
Pages (from-to)14303-14315
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number21
DOIs
StatePublished - May 22 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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