The Caenorhabditis elegans ekl (Enhancer of ksr-1 Lethality) Genes Include Putative Components of a Germline Small RNA Pathway

A canonical Ras-ERK signaling pathway specifies the fate of the excretory duct cell during Caenorhabditis elegans embryogenesis. The paralogs ksr-1 and ksr-2 encode scaffolding proteins that facilitate signaling through this pathway and that act redundantly to promote the excretory duct fate. In a genomewide RNAi screen for genes that, like ksr-2, are required in combination with ksr-1 for the excretory duct cell fate, we identified 16 "ekl" (enhancer of ksr-1 lethality) genes that are largely maternally required and that have molecular identities suggesting roles in transcriptional or post-transcriptional gene regulation. These include the Argonaute gene csr-1 and a specific subset of other genes implicated in endogenous small RNA processes, orthologs of multiple components of the NuA4/Tip60 histone acetyltransferase and CCR4/NOT deadenylase complexes, and conserved enzymes involved in ubiquitination and deubiquitination. The identification of four small RNA regulators (csr-1, drh-3, ego-1, and ekl-1) that share the Ekl phenotype suggests that these genes define a functional pathway required for the production and/or function of particular germline small RNA(s). These small RNAs and the other ekl genes likely control the expression of one or more regulators of Ras-ERK signaling that function at or near the level of kinase suppressor of Ras (KSR).