A Directed RNAi Screen Based on Larval Growth Arrest Reveals New Modifiers of <em>C. elegans</em> Insulin Signaling

<div><p>Genes regulating <em>Caenorhabditis elegans</em> insulin/IGF signaling (IIS) have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1) diapause, which is also influenced by <em>asna-1</em>, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the <em>asna-1</em> phenotype. Eighty- six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for <em>asna-1</em>-like larval arrest. <em>ykt-6</em>, <em>mrps-2</em>, <em>mrps-10</em> and <em>mrpl-43</em> were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in <em>C. elegans</em>.</p>