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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 hr 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.

SUBMITTER: Kelliher CM 

PROVIDER: S-EPMC7746235 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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PRD-2 directly regulates <i>casein kinase I</i> and counteracts nonsense-mediated decay in the Neurospora circadian clock.

Kelliher Christina M CM   Lambreghts Randy R   Xiang Qijun Q   Baker Christopher L CL   Loros Jennifer J JJ   Dunlap Jay C JC  

eLife 20201209


Circadian clocks in fungi and animals are driven by a functionally conserved transcription-translation feedback loop. In <i>Neurospora crassa</i>, 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 <i>prd-2</i> (<i>period-2</i>) gene, whose mutation is characterized by recessive inheritance of a long 26 hr perio  ...[more]

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