The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation

Yool Lee; Yang Shen; Lauren J Francey; Chidambaram Ramanathan; Amita Sehgal; Andrew C Liu; John B Hogenesch

doi:10.1038/s41598-019-48341-8

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The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation

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The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation

Yool Lee, Yang Shen, Lauren J Francey, Chidambaram Ramanathan, Amita Sehgal, Andrew C Liu and John B Hogenesch

Scientific reports, Vol.9(1), 11883

08/15/2019

DOI: https://doi.org/10.1038/s41598-019-48341-8

PMID: 31417156

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Abstract

Calcium Signaling

Cell Line

Cell Nucleus - metabolism

Circadian Clocks - physiology

Circadian Rhythm - physiology

CLOCK Proteins - genetics

CLOCK Proteins - metabolism

Cryptochromes - metabolism

Gene Expression Regulation

Gene Knockdown Techniques

Models, Biological

Period Circadian Proteins - metabolism

Protein Transport

RNA Interference

RNA, Long Noncoding - genetics

Signal Transduction

Post-translational regulation plays a central role in the circadian clock mechanism. However, nucleocytoplasmic translocation of core clock proteins, a key step in circadian timekeeping, is not fully understood. Earlier we found that the NRON scaffolding complex regulates nuclear translocation of NFAT and its signaling. Here, we show that components of the NRON complex also regulate the circadian clock. In peripheral cell clock models, genetic perturbation of the NRON complex affects PER and CRY protein nuclear translocation, dampens amplitude, and alters period length. Further, we show small molecules targeting the NFAT pathway alter nuclear translocation of PER and CRY proteins and impact circadian rhythms in peripheral cells and tissue explants of the master clock in the suprachiasmatic nucleus. Taken together, these studies highlight a key role for the NRON complex in regulating PER/CRY subcellular localization and circadian timekeeping.

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Title: The NRON complex controls circadian clock function through regulated PER and CRY nuclear translocation
Creators: Yool Lee - Washington State University, Biomedical Sciences, Department of
Yang Shen - Florida College
Lauren J Francey - Cincinnati Children's Hospital Medical Center
Chidambaram Ramanathan - University of Memphis
Amita Sehgal - University of Pennsylvania
Andrew C Liu - Department of Biological Sciences, University of Memphis, Memphis, TN, 38152, USA
John B Hogenesch - Cincinnati Children's Hospital Medical Center
Publication Details: Scientific reports, Vol.9(1), 11883
Academic Unit: Elson S. Floyd College of Medicine
Grant note: R01 NS054794 / NINDS NIH HHS
Identifiers: 99901132535801842
Language: English
Resource Type: Journal article