Alternative splicing coupled mRNA decay shapes the temperature‐dependent transcriptome

• Published in: EMBO reports 2020-12, Vol.21 (12), p.e51369-n/a
• Main Authors: Neumann, Alexander, Meinke, Stefan, Goldammer, Gesine, Strauch, Miriam, Schubert, Daniel, Timmermann, Bernd, Heyd, Florian, Preußner, Marco
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Ambient temperature; Animals; Biological clocks; Body temperature; circadian clock; Circadian rhythm; Circadian rhythms; Decay; EMBO09; EMBO36; Evolutionary conservation; Exons; Exons - genetics; Gene expression; Kinases; Mammals; mRNA decay; mRNA turnover; NMD; Nonsense Mediated mRNA Decay; Phosphorylation; Proteins; RNA-binding protein; Splicing; SR proteins; Temperature; Temperature control; Temperature dependence; Transcriptome
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.202051369

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. Synopsis This study identifies temperature‐controlled splicing variants triggering nonsense‐mediated decay and evolutionary conserved exons mediating temperature‐controlled gene expression levels, indicating that circadian and seasonal temperature signals feed into global gene expression control. SR‐proteins from plants to human show temperature‐controlled AS‐NMD. Temperature‐controlled AS‐NMD represents a second circadian clock‐independent generator of global rhythms. This mechanism allows for the systemic integration of daily and seasonal temperature changes. Graphical Abstract This study identifies temperature‐controlled splicing variants triggering nonsense‐mediated decay and evolutionary conserved exons mediating temperature‐controlled gene expression levels, indicating that circadian and seasonal temperature signals feed into global gene expression control.