Understanding recursive splicing in the human genome

Abstract

Recursive splicing is a non-canonical splicing mechanism that results in an intron being removed in two or more segments. Identifying recursive splicing presents technical challenges due to the lack of evidence in mRNA and the instability of splicing intermediates and byproducts. Few recursive splice sites have been identified with high confidence in human introns and largely have been located within long introns. Using a stringent approach to map lariat reads, I identified recursive splicing genome-wide, finding evidence for 100 new recursive splice sites in a broader range of intron sizes than previously reported and characterizing a new location for recursive splicing at the distal end of cassette exons. These data demonstrate the unappreciated prevalence of recursive splicing, the potential for finding additional sites as appropriately enriched RNA sequencing datasets become available, and its possible influence on gene expression through alternative exon isoforms. In addition, I discuss the evidence for intronic and distal exonic recursive splice sites as a mechanism of exon birth.