Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA.
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.
Heinrich
Bettina
B
Institute for Biochemistry, University of Erlangen, Fahrstrasse 17, 91054 Erlangen, Germany.
Zhang
Zhaiyi
Z
Raitskin
Oleg
O
Hiller
Michael
M
Benderska
Natalya
N
Hartmann
Annette M
AM
Bracco
Laurent
L
Elliott
David
D
Ben-Ari
Shani
S
Soreq
Hermona
H
Sperling
Joseph
J
Sperling
Ruth
R
Stamm
Stefan
S
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
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; C541737:RBMX protein, rat; D012322:RNA Precursors; D022821:RNA Splice Sites