Frequent fliers will have experienced how the body adapts to a different time zone and develops a new sleeping pattern, but the role of the body clock extends far beyond restless nights and jet lag. Publishing in Cell, a team of scientists in the USA describe how the circadian clock is linked to the control of protein synthesis — a fundamental life process in all cells.

Evolution has provided diverse life forms with daily behaviour and biological processes that change over 24 hour time scales, commonly known as a circadian rhythm. In animals, a collection of so-called clock genes control a range of physiological and metabolic processes including regulation of body temperature and hormone release. In particular, a protein called BMAL1 is vital for healthy behaviour of the circadian clock.

Jonathan Lipton and Mustafa Sahin at Boston Children’s Hospital and their collaborators identified over 300 proteins that interact with BMAL1 inside cells. Analysis showed that it associates preferentially with the biological machinery that translates genetic information into proteins, which are essential macromolecules with a vast range of functions.

An enzyme called S6K1 is a key component of a signalling pathway that regulates protein synthesis in response to the environment and surrounding stimuli. S6K1 modifies the structure of BMAL1 by phosphorylating a particular amino acid to give phospho-BMAL1. This modification is crucial for BMAL1 to stimulate protein synthesis, as without it BMAL1 is unable to bind to the translational machinery.

BMAL1 rhythmically associates with this machinery in synchrony with its phosphorylation by S6K1. In fact protein synthesis rates also demonstrate a circadian rhythm, highest during the active period of the day. It is thought that these processes could be the mechanism used by the body to convey different information to the translational machinery throughout the day.

The exact origins of circadian information in cells is still an open question, and there remains much to be learned about the contribution of BMAL1 to the body clock and wider disease. Nevertheless, these findings are a key step in linking circadian timing to the regulation of protein synthesis. Preliminary results already implicate phosphorylation of BMAL1 by S6K1 in the proliferation of breast cancer, raising hopes that further study will form the basis of future treatments in this area.

For further information

Read the Cell original research article which this summary is based on The Circadian Protein BMAL1 Regulates Translation in Response to S6K1-Mediated Phosphorylation (May 2015).

Visit the profile of the research ambassador, Sean Bartlett, who wrote this summary.

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