Who is to thank for the rhythms of my tail? – A mathematical study of circadian rhythmicity in poly(A) tail length

Dr. Jing Chen is a mathematical biologist. Her highly interdisciplinary educational path has shaped her interdisciplinary research interests. She got her B.S. degree in biology in 2002 from Fudan University in China. After that, she got her M.S. degree in mathematics in biosciences in 2004 from Technical University of Munich in Germany. In 2010, she earned her PhD degree in biophysics from UC Berkeley. Dr. Chen is interested in building mathematical models for intriguing biological problems, especially problems involving temporal, spatial and/or mechanical dynamics. Her research topics have spanned across many sub-areas of biology, including mitotic signaling, spindle assembly, bacterial motility, microbial population dynamics, and so on. Gene expression dynamics is one of the latest adventures of hers. Her research philosophy is to ask right questions and build suitable models.

The biological circadian clock aligns bodily functions to the day-and-night cycle and is important for organismal health. The rhythms in various biological processes ultimately stem from rhythmic gene expression in each single cell. Because several proteins in the mammalian core clock machinery are transcription factors, studies of mammalian circadian gene expression have focused on rhythmic transcriptional control. However, many recent studies suggested the importance of rhythmic post-transcriptional controls. Here we use mathematical modeling to investigate how transcriptional and post-transcriptional rhythms coordinately control rhythmic gene expression. We particularly focus on rhythmic post-transcriptional regulation of the mRNA poly(A) tail, a nearly universal feature of mRNAs which controls mRNA stability and translation. Our model reveals that the rhythmicities in poly(A) tail length and mRNA translatability are most strongly affected by of deadenylation, the process that shortens the poly(A) tail. Particularly, the phases of poly(A) tail length and mRNA translatability are dominated by the phase of deadenylation. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.

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