RNA-Binding Proteins MSI-1 (Musashi) and EXC-7 (HuR) Regulate Serotonin-Mediated Behaviors in C. elegans

Abstract

The evolutionarily conserved RNA-binding proteins HuR and MSI are essential for multiple developmental processes and are upregulated in many cancer tissues. The C. elegans homologues EXC-7 (HuR) and MSI-1 (MSI1 and MSI2) have been implicated in tubulogenesis, neural development, and specific behaviors that include male tail-curling to maintain contact with the hermaphrodite during mating. This behavior is mediated by serotonin signaling. Here, drug studies plus biochemical and genetic results indicate that MSI-1 affects serotonergic signaling through stabilization of mRNA of the G protein GOA-1/GNAO1 in neurons, which in turn affects activity of the serotonin synthase TPH-1/tryptophan hydroxylase via the response element CRH-1/CREB. EXC-7 (HuR) is also involved in this regulatory pathway. These results indicate a novel pathway and role for these RNA-binding proteins in regulating neurotransmitter levels that could be conserved in other tissues where these RNA-binding proteins are present.\n\nImpact Statement\n\nRNA-binding proteins Musashi and HuR upregulate serotonin levels for male-specific movement during mating via a novel pathway involving a neural G protein, response element, and serotonin synthase.