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Free keywords:
alternative splicing; circadian clock; mRNA decay; NMD; SRproteins; temperature
Abstract:
Mammalian body temperature oscillates with the time of the dayand is altered in diverse pathological conditions. We recently iden-tified a body temperature-sensitive thermometer-like kinase,which alters SR protein phosphorylation and thereby globallycontrols alternative splicing (AS). AS can generate unproductivevariants which are recognized and degraded by diverse mRNAdecay pathways—including nonsense-mediated decay (NMD). Herewe show extensive coupling of body temperature-controlled AS tomRNA decay, leading to global control of temperature-dependentgene expression (GE). Temperature-controlled, decay-inducingsplicing events are evolutionarily conserved and pervasively foundwithin RNA-binding proteins, including most SR proteins. AS-coupledpoison exon inclusion is essential for rhythmic GE of SR proteins andhas a global role in establishing temperature-dependent rhythmicGE profiles, both in mammals under circadian body temperaturecycles and in plants in response to ambient temperature changes.Together, these data identify body temperature-driven AS-coupledmRNA decay as an evolutionary ancient, core clock-independentmechanism to generate rhythmic GE.
