Recursive splicing is a rare event in the mouse brain

Abstract

Recursive splicing (RS) is a splicing mechanism to remove long introns from messenger RNA precursors of long genes. Compared to the hundreds of RS events identified in humans and drosophila, only ten RS events have been reported in mice. To further investigate RS in mice, we analyzed RS in the mouse brain, a tissue that is enriched in the expression of long genes. We found that nuclear total RNA sequencing is an efficient approach to investigate RS events. We analyzed 1.15 billion uniquely mapped reads from the nuclear total RNA sequencing data in the mouse cerebral cortex. Unexpectedly, we only identified 20 RS sites, suggesting that RS is a rare event in the mouse brain. We also identified that RS is constitutive between excitatory and inhibitory neurons and between sexes in the mouse cerebral cortex. In addition, we found that the primary sequence context is associated with RS splicing intermediates and distinguishes RS AGGT site from non-RS AGGT sites, indicating the importance of the primary sequence context in RS sites. Moreover, we discovered that cryptic exons may use an RS-like mechanism for splicing. Overall, we provide novel findings about RS in long genes in the mouse brain.

Therapeutic strategies for aberrant splicing in cancer and genetic disorders

“…In addition to the conventional splicing described above, which involves the one‐time removal of introns, there is a remarkable phenomenon known as recursive splicing (RS). This process enables a multistep intron removal and has been identified in Drosophila, 20 mice, 21 and humans, 22 highlighting its biological significance. The mechanics of RS are depicted in Figure 1.…”