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Alternative splicing coupled mRNA decay shapes the temperature-dependent transcriptome


ABSTRACT: Mammalian body temperature oscillates with the time of the day and is altered in diverse pathological conditions. We recently identified a body temperature-sensitive thermometer-like kinase, which alters SR protein phosphorylation and thereby globally controls alternative splicing (AS). AS can generate unproductive variants which are recognized and degraded by diverse mRNA decay pathways - including nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to mRNA decay, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled, decay-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. AS-coupled poison exon inclusion is essential for rhythmic GE of SR proteins and has a global role in establishing temperature-dependent rhythmic GE profiles, both, in mammals under circadian body temperature cycles and in plants in response to ambient temperature changes. Together, these data identify body temperature-driven AS coupled mRNA decay as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.

SUBMITTER: Dr. Alexander Neumann 

PROVIDER: S-SCDT-EMBOR-2020-51369-T | biostudies-other |

REPOSITORIES: biostudies-other

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