PRD-2 directly regulates casein kinase I and counteracts nonsense mediated decay in the Neurospora circadian clock
- Geisel School of Medicine at Dartmouth, United States
- 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
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RNA-seq analysis of wild type and upf1 knockout strains in the filamentous fungus Neurospora crassaNCBI Gene Expression Omnibus, GSE97157.
Article and author information
Author details
Christina M Kelliher
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
- Detlef Weigel, Max Planck Institute for Developmental Biology, Germany
Publication history
- Received: October 14, 2020
- Accepted: December 8, 2020
- Accepted Manuscript published: December 9, 2020 (version 1)
- Version of Record published: December 17, 2020 (version 2)
- 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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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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