Abstract:
:Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing the small temperature differentials leading to temperature-dependent sex determination (TSD) in poikilothermic reptiles has not been identified. Here, we show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes, which is conferred by structural rearrangements within the kinase activation segment. Lower body temperature activates CLKs resulting in strongly increased phosphorylation of SR proteins in vitro and in vivo. This globally controls temperature-dependent alternative splicing and gene expression, with wide implications in circadian, tissue-specific, and disease-associated settings. This temperature sensor is conserved across evolution and adapted to growth temperatures of diverse poikilotherms. The dynamic temperature range of reptilian CLK homologs suggests a role in TSD.
journal_name
Mol Celljournal_title
Molecular cellauthors
Haltenhof T,Kotte A,De Bortoli F,Schiefer S,Meinke S,Emmerichs AK,Petermann KK,Timmermann B,Imhof P,Franz A,Loll B,Wahl MC,Preußner M,Heyd Fdoi
10.1016/j.molcel.2020.01.028subject
Has Abstractpub_date
2020-04-02 00:00:00pages
57-69.e4issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(20)30049-6journal_volume
78pub_type
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