Recursive splicing is a rare event in the mouse brain

Abstract

SummaryRecursive splicing (RS) is a mechanism to excise long introns from messenger RNA precursors. We focused on nuclear RNA, which is enriched for RS splicing intermediates and nascent transcripts, to investigate RS in the mouse brain. We identified new RS sites and discovered that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. Moreover, we found that the primary sequence context, including the U1 snRNA binding site, the polypyrimidine tract, and a strong 3’ splice site, determines RS sites in long introns. We also uncovered a new type of exon-like RS events termed exonicRS that may represent an intermediate stage of RS sites evolving into annotated exons. Furthermore, the strengths of 5’ splice sites are able to classify RS events into RS sites and exonicRS. Overall, these findings provide mechanistic insights into the splicing and evolution of long genes.