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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.
Pubmed ID: 32059760
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A Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsSoftware tool for analysis of Alternative Splicing events and calculation of weighted transcripts per million values TPM on gene level. RNA-seq analysis method that quantifies AS events of any complexity without loss of accuracy. Used for accurate profiling AS to find misregulation present in human diseases.
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View all literature mentionsCell line TH-1 subline B1 is a Spontaneously immortalized cell line with a species of origin Terrapene carolina (Eastern box turtle)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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