AbstractThe alternatively spliceddaf-2btranscript inCaenorhabditis elegansencodes a truncated isoform of the nematode insulin receptor that retains the extracellular ligand binding domain but lacks the intracellular signaling domain and is therefore unable to transduce a signal. To identify factors that influence expression ofdaf-2b, we performed a targeted RNA interference screen ofrspgenes, which encode splicing factors from the serine/arginine protein family. Loss ofrsp-2significantly increased the expression of a fluorescentdaf-2bsplicing reporter, as well as increasing expression of endogenousdaf-2btranscripts. Correspondingly,rsp-2mutants exhibited similar phenotypes to those previously observed with DAF-2B overexpression, namely suppression of pheromone-induced dauer formation, enhancement of dauer entry in insulin signaling mutants, inhibition of dauer recovery, and increased lifespan. However, the epistatic relationship betweenrsp-2anddaf-2bvaried according to the experimental context. Increased dauer entry and delayed dauer exit ofrsp-2mutants in an insulin signaling mutant background were partially dependent ondaf-2b. Conversely, suppression of pheromone-induced dauer formation and increased lifespan inrsp-2mutants were independent ofdaf-2b.These data demonstrate thatC. elegansRSP-2, an ortholog of human splicing factor protein SRSF5/SRp40, is involved in regulating the expression of the truncated DAF-2B isoform. However, we also find that RSP-2 can influence dauer formation and lifespan independently of DAF-2B.