RBM-5 modulates U2AF large subunit-dependent alternative splicing in <i>C. elegans</i>

A key step in pre-mRNA splicing is the recognition of 3ʹ splicing sites by the U2AF large and small subunits, a process regulated by numerous <i>trans</i>-acting splicing factors. How these <i>trans</i>-acting factors interact with U2AF <i>in vivo</i> is unclear. From a screen for suppressors of the temperature-sensitive (ts) lethality of the <i>C. elegans</i> U2AF large subunit gene <i>uaf-1(n4588)</i> mutants, we identified mutations in the RNA binding motif gene <i>rbm-5</i>, a homolog of the tumor suppressor gene <i>RBM5. rbm-5</i> mutations can suppress <i>uaf-1(n4588)</i> ts-lethality by loss of function and neuronal expression of <i>rbm-5</i> was sufficient to rescue the suppression. Transcriptome analyses indicate that <i>uaf-1(n4588)</i> affected the expression of numerous genes and <i>rbm-5</i> mutations can partially reverse the abnormal gene expression to levels similar to that of wild type. Though <i>rbm-5</i> mutations did not obviously affect alternative splicing per se, they can suppress or enhance, in a gene-specific manner, the altered splicing of genes in <i>uaf-1(n4588)</i> mutants. Specifically, the recognition of a weak 3ʹ splice site was more susceptible to the effect of <i>rbm-5</i>. Our findings provide novel <i>in vivo</i> evidence that RBM-5 can modulate UAF-1-dependent RNA splicing and suggest that RBM5 might interact with U2AF large subunit to affect tumor formation.