Pervasive changes of mRNA splicing in <i>upf1</i> -deficient zebrafish identify <i>rpl10a</i> as a regulator of T cell development
Divine-Fondzenyuy Lawir, Katarzyna Sikora, Connor P. O’Meara, Michael Schorpp, Thomas Boehm
Abstract
Significance Random errors and genetic lesions give rise to messenger RNAs encoding nonfunctional or toxic protein variants. An evolutionarily conserved cellular surveillance mechanism recognizes such aberrant transcripts and subjects them to destruction, a process known as nonsense-mediated decay (NMD). The UPF1 protein is an essential component of this NMD machinery. In a genetic screen aimed at identifying regulators of T cell development in zebrafish, we discovered a upf1 mutation that causes widespread changes in the patterns of pre-mRNA splicing. Among the mRNA splicing regulators whose transcripts were affected by the mutation, the noncanonical splicing factor rpl10a was identified as a determinant of T cell development, exemplifying the advantages of examining NMD deficiency in the context of the whole vertebrate organism.