Bmal1 integrates circadian function and temperature sensing in the suprachiasmatic nucleus

Author:

Hoekstra Marieke M. B.12ORCID,Ness Natalie12ORCID,Badia-Soteras Aina12ORCID,Brancaccio Marco12ORCID

Affiliation:

1. Department of Brain Science, Imperial College London, London W12 0NN, United Kingdom

2. Department of Brain Sciences, United Kingdom Dementia Research Institute at Imperial College London, London W12 0NN, United Kingdom

Abstract

Circadian regulation and temperature dependency are important orchestrators of molecular pathways. How the integration between these two drivers is achieved, is not understood. We monitored circadian- and temperature-dependent effects on transcription dynamics of cold-response protein RNA Binding Motif 3 (Rbm3). Temperature changes in the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), induced Rbm3 transcription and regulated its circadian periodicity, whereas the core clock gene Per2 was unaffected. Rbm3 induction depended on a full Brain And Muscle ARNT-Like Protein 1 (Bmal1) complement: reduced Bmal1 erased Rbm3 responses and weakened SCN circuit resilience to temperature changes. By focusing on circadian and temperature dependency, we highlight weakened transmission between core clock and downstream pathways as a potential route for reduced circadian resilience.

Funder

UK Dementia Research Institute

Imperial College London

Swiss National Science Foundation

Publisher

Proceedings of the National Academy of Sciences

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