No 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 concentrationdependent 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 sexspecific expression of hnRNP G and RBMY, could contribute to molecular sex differences in mammals.All protein-coding genes undergo pre-mRNA processing, and the large majority of these genes are alternatively spliced (1). Alternative exons can change many functional aspects of mRNAs and their encoded proteins. The best understood functions are stop codons or frameshifts that are introduced by 20 -35% of alternative exons, which often destine the altered mRNA to nonsense-mediated decay. Examples described in the literature show that alternative splicing regulates the binding properties, intracellular localization, enzymatic activity, protein stability, and post-translational modifications of a large number of proteins (reviewed in Ref.2). Thus, it appears that alternative pre-mRNA processing is a key mechanism regulating the gene expression of complex organisms by generating multiple mRNA isoforms, which encode functionally diverse proteins. Despite its importance, the exact mechanisms governing splice site selection are still poorly understood. In vertebrate systems, protein complexes assemble transiently on exons, and their interaction with the splicing machinery as well as RNA-RNA interactions between spliceosomal proteins and pre-mRNA determine whether an exon is included or skipped (reviewed in Refs. 3 and 4).When isolated from nuclei of mammalian cells, RNA polymerase II transcripts are found assembled in large ribonucleoprotein 21-MDa complexes, the supraspliceosome, composed of all five spliceosomal small nuclear ribonucleoproteins as well as additional proteins. The entire repertoire of nuclear pre-mRNAs, independent of their length or number of introns, is individually found assembled in supraspliceosomes (reviewed in Ref. 5). Structural studies revealed that the supraspliceosome is composed of four substructure...

LifeMap Discovery™ provides investigators with an integrated database of embryonic development, stem cell biology and regenerative medicine. The hand-curated reconstruction of cell ontology with stem cell biology; including molecular, cellular, anatomical and disease-related information, provides efficient and easy-to-use, searchable research tools. The database collates in vivo and in vitro gene expression and guides translation from in vitro data to the clinical utility, and thus can be utilized as a powerful tool for research and discovery in stem cell biology, developmental biology, disease mechanisms and therapeutic discovery. LifeMap Discovery is freely available to academic nonprofit institutions at http://discovery.lifemapsc.com

No abstract

No abstract