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

ABSTRACT:

Background

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.

Methods

We calculated genetic constraint of the identified motif in 125 748 exomes collected from the gnomAD database. Furthermo

SUBMITTER: Tijsen AJ 

PROVIDER: S-EPMC8032209 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature