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

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Abstract
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).