Cx26 keratitis ichthyosis deafness syndrome mutations trigger alternative splicing of Cx26 to prevent expression and cause toxicity <i>in vitro</i>.

ABSTRACT: The Cx26 mRNA has not been reported to undergo alternative splicing. In expressing a series of human keratitis ichthyosis deafness (KID) syndrome mutations of Cx26 (A88V, N14K and A40V), we found the production of a truncated mRNA product. These mutations, although not creating a cryptic splice site, appeared to activate a pre-existing cryptic splice site. The alternative splicing of the mutant Cx26 mRNA could be prevented by mutating the predicted 3', 5' splice sites and the branch point. The presence of a C-terminal fluorescent protein tag (mCherry or Clover) was necessary for this alternative splicing to occur. Strangely, Cx26^A88V could cause the alternative splicing of co-expressed WT Cx26-suggesting a trans effect. The alternative splicing of Cx26^A88V caused cell

SUBMITTER: Cook J 

PROVIDER: S-EPMC6731697 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature