2018年12月1日
Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization
Scientific Reports
- 巻
- 8
- 号
- 1
- 開始ページ
- 8970
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41598-018-26624-w
- 出版者・発行元
- Nature Publishing Group
RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study.
- リンク情報
-
- DOI
- https://doi.org/10.1038/s41598-018-26624-w
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/29895960
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85048788642&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85048788642&origin=inward
- ID情報
-
- DOI : 10.1038/s41598-018-26624-w
- ISSN : 2045-2322
- eISSN : 2045-2322
- PubMed ID : 29895960
- SCOPUS ID : 85048788642