1. Cell Biology
  2. Genetics and Genomics
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KPNB1 mediates PER/CRY nuclear translocation and circadian clock function

  1. Yool Lee
  2. A Reum Jang
  3. Lauren J Francey
  4. Amita Sehgal
  5. John B Hogenesch  Is a corresponding author
  1. Perelman School of Medicine at the University of Pennsylvania, United States
  2. Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, United States
Research Article
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Cite this article as: eLife 2015;4:e08647 doi: 10.7554/eLife.08647

Abstract

Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of NFAT (NRON) ribonucleoprotein (RNP) complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 trapped the PER/CRY complex in cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacted mainly with PER proteins and directed PER/CRY nuclear transport in circadian fashion. Interestingly, KPNB1 regulated the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolished behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of circadian clock.

Article and author information

Author details

  1. Yool Lee

    Department of Systems Pharmacology and Translational Therapeutics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. A Reum Jang

    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lauren J Francey

    Department of Systems Pharmacology and Translational Therapeutics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amita Sehgal

    Department of Neuroscience, Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. John B Hogenesch

    Department of Systems Pharmacology and Translational Therapeutics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States
    For correspondence
    hogenesc@mail.med.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Achim Kramer

Publication history

  1. Received: May 11, 2015
  2. Accepted: August 28, 2015
  3. Accepted Manuscript published: August 29, 2015 (version 1)
  4. Version of Record published: October 8, 2015 (version 2)

Copyright

© 2015, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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