Titin Circular RNAs Create a Back-Splice Motif Essential for SRSF10 Splicing | Zendy

Anke J. Tijsen | Zendy; Lucia Ortega | Zendy; Yolan J. Reckman | Zendy; Xiaolei Zhang | Zendy; Ingeborg van der Made | Zendy; Simona Aufiero | Zendy; Jiuru Li | Zendy; Selina C. Kamps | Zendy; Anouk van den Bout | Zendy; Harsha D. Devalla | Zendy; Karin Y. van SpaendonckZwarts | Zendy; Stefan Engelhardt | Zendy; Lior Gepstein | Zendy; James S. Ware | Zendy; Yigal M. Pinto | Zendy

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Titin Circular RNAs Create a Back-Splice Motif Essential for SRSF10 Splicing

Author(s) -

Anke J. Tijsen,

Lucia Ortega,

Yolan J. Reckman,

Xiaolei Zhang,

Ingeborg van der Made,

Simona Aufiero,

Jiuru Li,

Selina C. Kamps,

Anouk van den Bout,

Harsha D. Devalla,

Karin Y. van SpaendonckZwarts,

Stefan Engelhardt,

Lior Gepstein,

James S. Ware,

Yigal M. Pinto

Publication year - 2021

Publication title -

circulation

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.795

H-Index - 607

eISSN - 1524-4539

pISSN - 0009-7322

DOI - 10.1161/circulationaha.120.050455

Subject(s) - titin , rna splicing , induced pluripotent stem cell , alternative splicing , genetics , microbiology and biotechnology , biology , sarcomere , gene , rna , myocyte , exon , embryonic stem cell

TTN (Titin), the largest protein in humans, forms the molecular spring that spans half of the sarcomere to provide passive elasticity to the cardiomyocyte. Mutations that disrupt the TTN transcript are the most frequent cause of hereditary heart failure. We showed before that TTN produces a class of circular RNAs (circRNAs) that depend on RBM20 to be formed. In this study, we show that the back-splice junction formed by this class of circRNAs creates a unique motif that binds SRSF10 to enable it to regulate splicing. Furthermore, we show that one of these circRNAs (cTTN1) distorts both localization of and splicing by RBM20.

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