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