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

Abstract

We demonstrate that circRNAs formed from the <i>TTN</i> transcript are essential for normal splicing of key muscle genes by enabling splice regulators RBM20 and SRSF10. This shows that the <i>TTN</i> transcript also has regulatory roles, besides its well-known signaling and structural function. In addition, we demonstrate that the specific sequence created by the back-splice junction of these circRNAs has important functions. This highlights the existence of functionally important sequences that cannot be recognized as such in the human genome but provides an as-yet unrecognized source for functional sequence variation.