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Science 338 (6105): 379-383

Copyright © 2012 by the American Association for the Advancement of Science

Cold-Inducible RNA-Binding Protein Modulates Circadian Gene Expression Posttranscriptionally

Jörg Morf,1 Guillaume Rey,2,* Kim Schneider,1 Markus Stratmann,1 Jun Fujita,3 Felix Naef,2 Ueli Schibler1,{dagger}

Abstract: In mammalian tissues, circadian gene expression can be driven by local oscillators or systemic signals controlled by the master pacemaker in the suprachiasmatic nucleus. We show that simulated body temperature cycles, but not peripheral oscillators, controlled the rhythmic expression of cold-inducible RNA-binding protein (CIRP) in cultured fibroblasts. In turn, loss-of-function experiments indicated that CIRP was required for high-amplitude circadian gene expression. The transcriptome-wide identification of CIRP-bound RNAs by a biotin-streptavidin–based cross-linking and immunoprecipitation (CLIP) procedure revealed several transcripts encoding circadian oscillator proteins, including CLOCK. Moreover, CLOCK accumulation was strongly reduced in CIRP-depleted fibroblasts. Because ectopic expression of CLOCK improved circadian gene expression in these cells, we surmise that CIRP confers robustness to circadian oscillators through regulation of CLOCK expression.

1 Department of Molecular Biology, University of Geneva, and National Centre of Competence in Research, Frontiers in Genetics, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland.
2 The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.
3 Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 605-8507, Japan.

* Present address: Department of Clinical Neurosciences, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK.

{dagger} To whom correspondence should be addressed: ueli.schibler{at}unige.ch


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