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Alternative splicing coupled nonsense-mediated decay shapes the temperature-dependent transcriptome

By Alexander Neumann, Stefan Meinke, Gesine Goldammer, Miriam Strauch, Daniel Schubert, Bernd Timmermann, Florian Heyd, Marco Preu├čner

Posted 21 Feb 2020
bioRxiv DOI: 10.1101/2020.02.19.956037

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 mRNA variants containing premature termination codons, which are degraded by nonsense-mediated decay (NMD). Here we show extensive coupling of body temperature-controlled AS to NMD, leading to global control of temperature-dependent gene expression (GE). Temperature-controlled NMD-inducing splicing events are evolutionarily conserved and pervasively found within RNA-binding proteins, including most SR proteins. NMD-inducing exons are essential for rhythmic GE of SR proteins and have 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-NMD as an evolutionary ancient, core clock-independent mechanism to generate rhythmic GE.

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