We have been studying a temperature-sensitive maternal effect lethal mutation,
or430, that results in small centrosomes, short, mis-oriented spindles and highly penetrant chromosome segregation defects during cell division in single-cell mutant embryos raised at the non-permissive temperature. In addition to defects in spindle morphology and orientation,
or430 has less penetrant defects in meiosis, pronuclear migration, cell cycle timing and polarity. Furthermore,
or430 larvae raised at to the non-permissive temperature have protruding vulvae and are uncoordinated. We mapped
or430 to a small region of chromosome IV. One predicted open reading frame within the region, F11A10.2, produces a similar phenotype when its function is reduced using RNA interference (micro-injection of dsRNA into the RNA interference-hypersensitive mutant background,
rrf-3; seeSimmer et al., Current Biology 12: 1317-1319 2002). We sequenced F11A10.2 in
or430 mutants and identified a mis-sense mutation,, suggesting that
or430 is an allele of F11A10.2. This gene is predicted to encode the only C. elegans homolog of the vertebrate Splicing Factor 3a, subunit 2. Splicing Factor 3a is a general splice factor and a component of the U2 small nuclear ribonucleoprotein particle (Brosi et al. Science 1993 Oct 1;262(5130):102-5). Given the molecular identity of the gene, we hypothesize that the early, plieotropic defects seen in
or430 embryos are due to disruption of a conserved, general splicing function for F11A10.2, thereby disrupting the expression of numerous maternally contributed proteins in the early embryo. Consistent with this hypothesis, we find reduced levels of several different proteins in
or430 mutants, including cytoplasmic, nuclear and centrosomal proteins.