In NF1, CFTR, PER3, CARS and SYT7, alternatively included exons show higher conservation of surrounding intron sequences than constitutive exons.

Abstract

It is still not fully understood to what extent intronic sequences contribute to the regulation of the different forms of alternative splicing. We are interested in the regulation of alternative cassette exon events, such as exon inclusion and exon skipping. We investigated these events by comparative genomic analysis of human and mouse in five experimentally well-characterized genes, neurofibromatosis 1 (NF1), cystic fibrosis transmembrane conductance regulator (CFTR), period 3 (PER3), cysteinyl-tRNA synthetase (CARS) and synaptotagmin 7 (SYT7). In NF1, high intron identity around the 52 constitutive and four alternatively skipped NF1 exons is restricted to the close vicinity of the exons. In contrast, we found on average high conservation of intron sequences over 300 base pairs up- and downstream of the five alternatively included NF1 exons. The investigation of alternatively included exons in CFTR, PER3, CARS and SYT7 supported this finding. In contrast, the mean intron identities around the alternatively skipped exons in CTFR and NF1 do not differ considerably from those around the constitutive exons. In these genes, the difference in intron conservation could point to a difference between the regulation of alternative exon inclusion and alternative exon skipping or constitutive exon splicing. Additional genome-wide investigations are necessary to elucidate to what extent our finding can be generalized.