The 5'-3' exoribonuclease xrn-1 is essential for ventral epithelial enclosure during C. elegans embryogenesis

Ribonucleases have been studied in yeast and bacteria, but their biological significance to multicellular organisms is virtually unknown. However, there is increasing evidence that specific, timed transcript degradation is critical for regulation of many cellular processes, including early development and RNA interference. In this report we have investigated the effects of the 5'-3' exoribonuclease xrn-1 on the development of the nematode worm Caenorhabditis elegans. Silencing of xrn-1 expression using RNA interference results in embryos that fail to complete ventral enclosure, where the outer layer of cells normally closes over the mesoderm in a purse-string movement. Our data suggest that xrn-1 is involved in a critical aspect of epithelial movement and reveal an unexpected link between RNA stability and morphogenesis. Because xrn-1 is highly conserved in all eukaryotes, it is possible that it plays a role in similar morphological processes such as dorsal or thorax closure in Drosophila and wound healing in humans. In contrast to work in human tissue culture cells, where the 3'-5' pathway has been shown to be the most important for degradation of mRNAs, our work shows that the 5'-3' degradation pathway is crucially important at a critical stage of development in C. elegans. We have also investigated whether xrn-1 can influence the response of C. elegans to RNA interference. Our data indicate that xrn-1 plays a facilitating, but not crucial role in this process.