PRD-2 directly regulates casein kinase I and counteracts nonsense mediated decay in the Neurospora circadian clock

  1. Christina M Kelliher
  2. Randy Lambreghts
  3. Qijun Xiang
  4. Christopher L Baker
  5. Jennifer J Loros
  6. Jay C Dunlap  Is a corresponding author
  1. Geisel School of Medicine at Dartmouth, United States
  2. The Jackson Laboratory, United States

Abstract

Circadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. In Neurospora crassa, negative feedback is executed by a complex of Frequency (FRQ), FRQ-interacting RNA helicase (FRH), and Casein Kinase I (CKI), which inhibits the activity of the clock's positive arm, the White Collar Complex (WCC). Here, we show that the prd-2 (period-2) gene, whose mutation is characterized by recessive inheritance of a long 26-hour period phenotype, encodes an RNA-binding protein that stabilizes the ck-1a transcript, resulting in CKI protein levels sufficient for normal rhythmicity. Moreover, by examining the molecular basis for the short circadian period of upf-1prd-6 mutants, we uncovered a strong influence of the Nonsense Mediated Decay pathway on CKI levels. The finding that circadian period defects in two classically-derived Neurospora clock mutants each arise from disruption of ck-1a regulation is consistent with circadian period being exquisitely sensitive to levels of casein kinase I.

Data availability

RNA-Sequencing data have been deposited in GEO under accession GSE155999

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Christina M Kelliher

    Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4554-1818
  2. Randy Lambreghts

    Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Qijun Xiang

    Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christopher L Baker

    Genetics and Genomics, The Jackson Laboratory, Bar Harbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jennifer J Loros

    Department of Biochemistry & Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jay C Dunlap

    Department of Molecular & Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, United States
    For correspondence
    jay.dunlap@Dartmouth.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1577-0457

Funding

National Institutes of Health (F32 GM128252)

  • Christina M Kelliher

National Institutes of Health (R35 GM118021)

  • Jay C Dunlap

National Institutes of Health (R35 GM118022)

  • Jennifer J Loros

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Detlef Weigel, Max Planck Institute for Developmental Biology, Germany

Publication history

  1. Received: October 14, 2020
  2. Accepted: December 8, 2020
  3. Accepted Manuscript published: December 9, 2020 (version 1)
  4. Version of Record published: December 17, 2020 (version 2)
  5. Version of Record updated: December 23, 2020 (version 3)

Copyright

© 2020, Kelliher 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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  1. Christina M Kelliher
  2. Randy Lambreghts
  3. Qijun Xiang
  4. Christopher L Baker
  5. Jennifer J Loros
  6. Jay C Dunlap
(2020)
PRD-2 directly regulates casein kinase I and counteracts nonsense mediated decay in the Neurospora circadian clock
eLife 9:e64007.
https://doi.org/10.7554/eLife.64007
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