Integrative analysis revealed the molecular mechanism underlying RBM10‐mediated splicing regulation. Issue 9 (22nd August 2013)

• Record Type: Journal Article
• Authors: Wang, Yongbo; Gogol‐Döring, Andreas; Hu, Hao; Fröhler, Sebastian; Ma, Yunxia; Jens, Marvin; Maaskola, Jonas; Murakawa, Yasuhiro; Quedenau, Claudia; Landthaler, Markus; Kalscheuer, Vera; Wieczorek, Dagmar; Wang, Yang; Hu, Yuhui; Chen, Wei
• Is Part Of: EMBO molecular medicine. Volume 5:Issue 9(2013:Sep.)
• Page Start: 1431
• Page End: 1442
• Publication Date: 2013-08-22
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201302663
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="emmm201302663-sec-0001" sec-type="section"> <p> <italic>RBM10</italic> encodes an RNA binding protein. Mutations in <italic>RBM10</italic> are known to cause multiple congenital anomaly syndrome in male humans, the TARP syndrome. However, the molecular function of RBM10 is unknown. Here we used PAR‐CLIP to identify thousands of binding sites of RBM10 and observed significant RBM10–RNA interactions in the vicinity of splice sites. Computational analyses of binding sites as well as loss‐of‐function and gain‐of‐function experiments provided evidence for the function of RBM10 in regulating exon skipping and suggested an underlying mechanistic model, which could be subsequently validated by minigene experiments. Furthermore, we demonstrated the splicing defects in a patient carrying an <italic>RBM10</italic> mutation, which could be explained by disrupted function of RBM10 in splicing regulation. Overall, our study established RBM10 as an important regulator of alternative splicing, presented a mechanistic model for RBM10‐mediated splicing regulation and provided a molecular link to understanding a human congenital disorder.</p> </sec> </abstract>