A novel species- and skeletal muscle specific microexon regulated by alternative splicing diversifies the menu of clathrin heavy chains in mice and rats

The existence of alternatively spliced microexons and their regulation have been greatly investigated in brain development and autism spectrum disorders, but very little is known about microexons in other tissues. We previously reported that a microexon (exon 31, 21 nt) in the essential clathrin heavy chain (CLTC) gene is developmentally regulated by alternative splicing specifically in striated muscles and this regulation is conserved between mice and humans.

CLTC protein is one of the two clathrin heavy chains that exist in humans, drives clathrin-mediated endocytosis and is required for the formation of the skeletal muscle contractile apparatus. Here, we report the discovery of another microexon in Cltc pre-mRNA (exon 33, 38 nt, herein referred to as microexon 33). Microexon 33 is the penultimate exon in Cltc gene and is exclusively included in mouse and rat adult skeletal muscles, encoding a premature stop codon that escapes nonsense-mediated decay.