American Journal of Pathology
American Journal of Pathology
5 years ago

Haploinsufficiency of hnRNP U changes activity pattern and metabolic rhythms

The neuropeptides arginine vasopressin (Avp) and vasoactive intestinal polypeptide (Vip) are critical for the communication and coupling of suprachiasmatic nucleus neurons, which organize daily rhythms of physiology and behavior in mammals. However, how these peptides are regulated remains uncharacterized. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein U (hnRNP U) is essential for the expression of Avp and Vip. Loss of one copy of the Hnrnpu gene resulted in fragmented locomotor activities and disrupted metabolic rhythms. Hnrnpu +/- mice were more active than wild-type mice in the day time but more inactive at night. These phenotypes were partially rescued by micro-infusion of Avp and Vip into free-moving animals. In addition, hnRNP U modulated Avp and Vip via directly binding to their promoters together with Bmal1: Clock heterodimers. Our work identifies hnRNP U as a novel regulator of the circadian pacemaker and provides new insights into the mechanism of rhythm output.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017306740

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