Global Profiling of Alternative Splicing Events and Gene Expression Regulated by HnRNPH/F

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Jan 4

PMID 23284676

Citations 35

Authors

Erming Wang

Vahid Aslanzadeh

Filomena Papa

Haiyan Zhu

Pierre De La Grange

Franca Cambi

Affiliations

Soon will be listed here.

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.

Citing Articles

Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.

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hnRNPs: roles in neurodevelopment and implication for brain disorders.

Tilliole P, Fix S, Godin J Front Mol Neurosci. 2024; 17:1411639.

PMID: 39086926 PMC: 11288931. DOI: 10.3389/fnmol.2024.1411639.

The Roles of hnRNP Family in the Brain and Brain-Related Disorders.

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Splicing regulation of GFPT1 muscle-specific isoform and its roles in glucose metabolisms and neuromuscular junction.

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The HNRNPF/H RNA binding proteins and disease.

Brownmiller T, Caplen N Wiley Interdiscip Rev RNA. 2023; 14(5):e1788.

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