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

Sci Rep. 2019 Aug 15;9(1):11883. doi: 10.1038/s41598-019-48341-8.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CLOCK Proteins / genetics
  • CLOCK Proteins / metabolism
  • Calcium Signaling
  • Cell Line
  • Cell Nucleus / metabolism*
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology
  • Cryptochromes / metabolism*
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Models, Biological
  • Period Circadian Proteins / metabolism*
  • Protein Transport
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Signal Transduction


  • Cryptochromes
  • NRON long noncoding RNA, human
  • Period Circadian Proteins
  • RNA, Long Noncoding
  • CLOCK Proteins