title: Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA.
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.
authors.affiliation: Institute for Biochemistry, University of Erlangen, Fahrstrasse 17, 91054 Erlangen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Heinrich
authors.forename: Zhaiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Oleg
authors.initials: O
authors.lastname: Raitskin
authors.forename: Michael
authors.initials: M
authors.lastname: Hiller
authors.forename: Natalya
authors.initials: N
authors.lastname: Benderska
authors.forename: Annette M
authors.initials: AM
authors.lastname: Hartmann
authors.forename: Laurent
authors.initials: L
authors.lastname: Bracco
authors.forename: David
authors.initials: D
authors.lastname: Elliott
authors.forename: Shani
authors.initials: S
authors.lastname: Ben-Ari
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
authors.forename: Joseph
authors.initials: J
authors.lastname: Sperling
authors.forename: Ruth
authors.initials: R
authors.lastname: Sperling
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005091:Exons / Q000235:genetics; D017930:Genes, Reporter; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012322:RNA Precursors / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D051381:Rats; D017381:Spliceosomes / Q000378:metabolism
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; C541737:RBMX protein, rat; D012322:RNA Precursors; D022821:RNA Splice Sites