C. elegans dss-1 is functionally conserved and required for oogenesis and larval growth

Abstract

<p>Abstract</p> <p>Background</p> <p>Dss1 (or Rpn15) is a recently identified subunit of the 26S proteasome regulatory particle. In addition to its function in the protein degradation machinery, it has been linked to BRCA2 (breast cancer susceptibility gene 2 product) and homologous DNA recombination, mRNA export, and exocytosis. While the fungal orthologues of Dss1 are not essential for viability, the significance of Dss1 in metazoans has remained unknown due to a lack of knockout animal models.</p> <p>Results</p> <p>In the current study deletion of <it>dss-1 </it>was studied in <it>Caenorhabditis elegans </it>with a <it>dss-1 </it>loss-of-function mutant and <it>dss-1 </it>directed RNAi. The analysis revealed an essential role for <it>dss-1 </it>in oogenesis. In addition, <it>dss-1 </it>RNAi caused embryonic lethality and larval arrest, presumably due to loss of the <it>dss-1 </it>mRNA maternal contribution. DSS-1::GFP fusion protein localised primarily in the nucleus. No apparent effect on proteasome function was found in <it>dss-1 </it>RNAi treated worms. However, expression of the <it>C. elegans dss-1 </it>in yeast cells deleted for its orthologue <it>SEM1 </it>rescued their temperature-sensitive growth phenotype, and partially rescued the accumulation of polyubiquitinated proteins in these cells.</p> <p>Conclusion</p> <p>The first knockout animal model for the gene encoding the proteasome subunit DSS-1/Rpn15/Sem1 is characterised in this study. In contrast to unicellular eukaryotes, the <it>C. elegans dss-1 </it>encodes an essential protein, which is required for embryogenesis, larval growth, and oogenesis, and which is functionally conserved with its yeast and human homologues.</p