PRD-2 directly regulates casein kinase I and counteracts nonsense-mediated decay in the Neurospora circadian clock.
PRD-2 directly regulates casein kinase I and counteracts nonsense-mediated decay in the Neurospora circadian clock.
复制标题
PRD-2直接调节酪蛋白激酶I，并抵消神经孢子般的时钟中胡说八道介导的衰变。
DOI：
10.7554/elife.64007
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发表时间：
2020-12-09
期刊：
影响因子：
7.7
通讯作者：
Dunlap JC
中科院分区：
文献类型：
--
作者：
Kelliher CM;Lambreghts R;Xiang Q;Baker CL;Loros JJ;Dunlap JC
真菌和动物的生物钟由功能保守的转录-翻译反馈环驱动。在粗糙脉孢菌中，负反馈由频率（FRQ）、FRQ相互作用RNA解旋酶（FRH）和酪蛋白激酶I（CKI）的复合物执行，其抑制时钟的正臂，即白色衣领复合物（WCC）的活性。在这里，我们表明，prd-2（周期-2）基因，其突变的特点是隐性遗传的长26小时周期表型，编码的RNA结合蛋白，稳定的CK-1A转录，导致CKI蛋白水平足以正常的节奏。此外，通过研究upf-1 prd-6突变体短昼夜节律的分子基础，我们发现无义介导的衰变途径对CKI水平有很强的影响。两种经典来源的脉孢菌时钟突变体的昼夜节律周期缺陷均由ck-1a调节的破坏引起，这一发现与昼夜节律周期对酪蛋白激酶I水平非常敏感一致。
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.