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

The biological circadian clock aligns our bodily functions to the day-and-night cycle and is important for our health. These bodily rhythms ultimately derive from rhythmic gene expression in individual cells. Because the core clock machinery includes several transcription factors, studies of circadian gene expression have long focused on rhythmic transcriptional control. However, recent studies suggest the importance of rhythmic post-transcriptional controls as well. One of such rhythmic controls occurs to the mRNA poly(A) tail, a nearly universal feature of mRNAs which controls mRNA stability and translation. Specifically, the length of poly(A) tail in many mRNAs are found to cycle over the day. In this work we constructed a parsimonious differential equation model to investigate how the length of poly(A) tail is rhythmically controlled. Because the dynamics of mRNA expression and poly(A) regulation can vary significantly among different genes, to understand the general properties of the modeled system we performed a variance-based global parameter sensitivity analysis on the model. Our analysis reveals that the rhythmicity of poly(A) tail length and mRNA translatability are most strongly affected by the rhythmicity of deadenylation, the process that shortens the poly(A) tail. Particularly, the phases of poly(A) tail length and mRNA translatability are strongly dominated by the phase of deadenylation, through which deadenylation could potentially serve to synchronize the rhythms of target gene expression. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.

Συνεδρία: 
Authors: 
Xiangyu Yao, Shihoko Kojima and Jing Chen
Room: 
5
Date: 
Monday, December 7, 2020 - 17:10 to 17:25

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