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Mol Cell. 2017 Aug 3;67(3):433-446.e4. doi: 10.1016/j.molcel.2017.06.006. Epub 2017 Jul 6.

Body Temperature Cycles Control Rhythmic Alternative Splicing in Mammals.

Author information

1
Laboratory of RNA Biochemistry, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 6, 14195 Berlin, Germany. Electronic address: mpreussner@zedat.fu-berlin.de.
2
Laboratory of RNA Biochemistry, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 6, 14195 Berlin, Germany.
3
Goethe University Frankfurt, Institute for Cell Biology and Neuroscience, Max-von-Laue-Strasse 13, 60438 Frankfurt am Main, Germany.
4
Laboratory of RNA Biochemistry, Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustrasse 6, 14195 Berlin, Germany. Electronic address: florian.heyd@fu-berlin.de.

Abstract

The core body temperature of all mammals oscillates with the time of the day. However, direct molecular consequences of small, physiological changes in body temperature remain largely elusive. Here we show that body temperature cycles drive rhythmic SR protein phosphorylation to control an alternative splicing (AS) program. A temperature change of 1°C is sufficient to induce a concerted splicing switch in a large group of functionally related genes, rendering this splicing-based thermometer much more sensitive than previously described temperature-sensing mechanisms. AS of two exons in the 5' UTR of the TATA-box binding protein (Tbp) highlights the general impact of this mechanism, as it results in rhythmic TBP protein levels with implications for global gene expression in vivo. Together our data establish body temperature-driven AS as a core clock-independent oscillator in mammalian peripheral clocks.

KEYWORDS:

SR proteins; Tbp; U2af; alternative splicing; body temperature; circadian clock; molecular thermometer; phosphorylation; splicing network

PMID:
28689656
DOI:
10.1016/j.molcel.2017.06.006
[Indexed for MEDLINE]
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