Caenorhabditis elegansAF4/FMR2 family homologaffl-2is required for heat shock induced gene expression

AbstractTo mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat shock induced gene expression inC. elegans, we identified a new allele ofhsf-1that alters its DNA-binding domain, and three additional alleles ofsup-45,a previously uncharacterized genetic locus. We identifiedsup-45as one of the two hitherto unknownC. elegansorthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamedsup-45asaffl-2(AF4/FMR2-Like).affl-2mutants are egg-laying defective and dumpy, but worms lacking its sole paralog (affl-1) appear wild-type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response.affl-2and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests thataffl-2may function downstream or parallel ofhsf-1. Our characterization ofaffl-2provides insights into the complex processes of transcriptional elongation and regulating heat shock induced gene expression to protect against heat stress.