PUF-8, a C. Elegans Ortholog of the RNA-binding Proteins PUM1 and PUM2, is Required for Robustness of the Cell Death Fate.

During C. elegans development, 1090 somatic cells are generated, of which 959 survive and 131 die, many through apoptosis. We present evidence that PUF-8, a C. elegans ortholog of the mammalian RNA-binding proteins PUM1 and PUM2, is required for the robustness of this 'survival and death' pattern. We found that PUF-8 prevents the inappropriate death of cells that normally survive, and we present evidence that this anti-apoptotic activity of PUF-8 is dependent on the ability of PUF-8 to interact with ced-3 (a C. elegans ortholog of caspase) mRNA, thereby repressing the activity of the pro-apoptotic ced-3 gene. PUF-8 also promotes the death of cells that are programmed to die, and we propose that this pro-apoptotic activity of PUF-8 may depend on the ability of PUF-8 to repress the expression of the anti-apoptotic ced-9 gene (a C. elegans ortholog of Bcl2). Our results suggest that stochastic differences in the expression of genes within the apoptosis pathway can disrupt the highly reproducible and robust survival and death pattern during C. elegans development, and that PUF-8 acts at the post-transcriptional level to level out these differences, thereby ensuring proper cell number homeostasis.