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

By Zhe Yang, Lan Lan, Xiaoqing Wu, Liang Xu, Matthew Buechner

Posted 27 Aug 2019
bioRxiv DOI: 10.1101/748509

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 Gα 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.

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