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Haploinsufficiency of hnRNP U Changes Activity Pattern and Metabolic Rhythms.

Authors
  • Lai, Beibei1
  • Zou, Jianghuan1
  • Lin, Zhaoyu1
  • Qu, Zhipeng1
  • Song, Anying1
  • Xu, Ying2
  • Gao, Xiang3
  • 1 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, China. , (China)
  • 2 Medical College of Soochou University, Suzhou, China. Electronic address: [email protected] , (China)
  • 3 State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Collaborative Innovation Center of Genetics and Development, Nanjing University, Nanjing, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
American Journal Of Pathology
Publisher
Elsevier
Publication Date
Jan 01, 2018
Volume
188
Issue
1
Pages
173–183
Identifiers
DOI: 10.1016/j.ajpath.2017.09.017
PMID: 29128567
Source
Medline
License
Unknown

Abstract

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. We found 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 daytime but more inactive at night. These phenotypes were partially rescued by microinfusion of Avp and Vip into free-moving animals. In addition, hnRNP U modulated Avp and Vip via directly binding to their promoters together with brain and muscle Arnt-like protein-1/circadian locomotor output cycles kaput heterodimers. Our work identifies hnRNP U as a novel regulator of the circadian pacemaker and provides new insights into the mechanism of rhythm output.

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