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Emerging roles for post-transcriptional regulation in circadian clocks

Abstract

Circadian clocks temporally organize behavior and physiology across the 24-h day. Great progress has been made in understanding the molecular basis of timekeeping, with a focus on transcriptional feedback networks that are post-translationally modulated. Yet emerging evidence indicates an important role for post-transcriptional regulation, from splicing, polyadenylation and mRNA stability to translation and non-coding functions exemplified by microRNAs. This level of regulation affects virtually all aspects of circadian systems, from the core timing mechanism and input pathways that synchronize clocks to the environment and output pathways that control overt rhythmicity. We hypothesize that post-transcriptional control confers on circadian clocks enhanced robustness as well as the ability to adapt to different environments. As much of what is known derives from nonneural cells or tissues, future work will be required to investigate the role of post-transcriptional regulation in neural clocks.

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Figure 1: Molecular and neural bases of circadian clocks and behaviors.
Figure 2: Nuclear post-transcriptional control of circadian clocks.
Figure 3: Cytoplasmic translational control of circadian clocks.
Figure 4: Cytoplasmic post-transcriptional control of circadian transcripts.

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Acknowledgements

We thank V. Kilman for helpful comments on the manuscript and M. Flourakis for providing an image in Figure 1d. This work was supported by the year of 2013 Research Fund (project no. 1.130009) and the 2013 Creativity & Innovation Research Fund (project no. 1.130036) of UNIST (Ulsan National Institute of Science and Technology) (C.L.) and by US National Institutes of Health NINDS (R01NS059042) and NIMH (R01MH 092273), and Defense Advanced Projects Research Agency (DARPA; D12AP00023) (R.A). R.A.'s effort is in part sponsored by DARPA, and the content of the information does not necessarily reflect the position or the policy of the Government and no official endorsement should be inferred.

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Correspondence to Chunghun Lim.

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Lim, C., Allada, R. Emerging roles for post-transcriptional regulation in circadian clocks. Nat Neurosci 16, 1544–1550 (2013). https://doi.org/10.1038/nn.3543

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