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Alterations of pre-mRNA splicing in human inflammatory bowel disease

Item Type:Article
Title:Alterations of pre-mRNA splicing in human inflammatory bowel disease
Creators Name:Haesler, R. and Kerick, M. and Mah, N. and Hultschig, C. and Richter, G. and Bretz, F. and Sina, C. and Lehrach, H. and Nietfeld, W. and Schreiber, S. and Rosenstiel, P.
Abstract:Alternative pre-mRNA splicing is regarded as a pivotal mechanism for generating proteome diversity and complexity from a limited inventory of mammalian genes. Aberrant splicing has been described as a predisposing factor for a number of diseases, but very little is known about its role in chronic inflammation. In this study, we systematically screened 149 splicing factors and 145 potential intron retention events for occurrence and differential expression in inflammatory bowel diseases (IBD). As a result, we identified 47 splicing factors and 33 intron retention events that were differentially regulated in mucosal tissue of IBD patients at transcript level. Despite the fact that Crohn's disease and ulcerative colitis, two subtypes of IBD, share the expression patterns of splicing factors and intron retention events in the majority of cases, we observed significant differences. To investigate these subtype-specific changes in detail we determined the expression levels of seven splicing factors (DUSP11, HNRPAB, HNRPH3, SLU7, SFR2IP, SFPQ, SF3B14) and three intron retention events (PARC, IER3, FGD2) in a cohort of 165 patients with inflammatory diseases of the colon (120 with IBD) and 30 healthy controls by real time PCR (TaqMan). This study demonstrates the potential impact of regulated splicing factors on subsequent regulated intron retention in the pathogenesis of chronic inflammation, exemplified by IBD.
Keywords:Splicing, Intron Retention, Inflammatory Bowel Disease, Ulcerative Colitis, Crohn's Disease, Animals, Mice
Source:European Journal of Cell Biology
Publisher:Wissenschaftliche Verlagsgesellschaft
Page Range:603-611
Date:June 2011
Official Publication:https://doi.org/10.1016/j.ejcb.2010.11.010
PubMed:View item in PubMed

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