title: Global profiling of alternative splicing events and gene expression regulated by hnRNPH/F.
abstract: In this study, we have investigated the global impact of heterogeneous nuclear Ribonuclear Protein (hnRNP) H/F-mediated regulation of splicing events and gene expression in oligodendrocytes. We have performed a genome-wide transcriptomic analysis at the gene and exon levels in Oli-neu cells treated with siRNA that targets hnRNPH/F compared to untreated cells using Affymetrix Exon Array. Gene expression levels and regulated exons were identified with the GenoSplice EASANA algorithm. Bioinformatics analyses were performed to determine the structural properties of G tracts that correlate with the function of hnRNPH/F as enhancers vs. repressors of exon inclusion. Different types of alternatively spliced events are regulated by hnRNPH/F. Intronic G tracts density, length and proximity to the 5' splice site correlate with the hnRNPH/F enhancer function. Additionally, 6% of genes are differently expressed upon knock down of hnRNPH/F. Genes that regulate the transition of oligodendrocyte progenitor cells to oligodendrocytes are differentially expressed in hnRNPH/F depleted Oli-neu cells, resulting in a decrease of negative regulators and an increase of differentiation-inducing regulators. The changes were confirmed in developing oligodendrocytes in vivo. This is the first genome wide analysis of splicing events and gene expression regulated by hnRNPH/F in oligodendrocytes and the first report that hnRNPH/F regulate genes that are involved in the transition from oligodendrocyte progenitor cells to oligodendrocytes.
authors.affiliation: Department of Neurology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Erming
authors.initials: E
authors.lastname: Wang
authors.forename: Vahid
authors.initials: V
authors.lastname: Aslanzadeh
authors.forename: Filomena
authors.initials: F
authors.lastname: Papa
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.forename: Franca
authors.initials: F
authors.lastname: Cambi
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000378:metabolism*; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H