Who Is to Thank for the Rhythms of My Tail? – A Mathematical Study of Circadian Rhythmicity in Poly(A) Tail Length

The circadian rhythm of our body ultimately derives from rhythmic gene expression in individual cells. As the core clock circuit includes several transcription factors with broad targets in the genome, studies of circadian gene expression have long focused on rhythmic transcriptional control. However, recent studies revealed the importance of rhythmic post-transcriptional controls. A notable one of such rhythmic controls occurs to the poly(A) tail of mRNAs, a nearly universal feature of mRNAs which controls mRNA stability and translation. In many mRNAs, the length of the poly(A) tail is found to oscillate over the day. In this work we constructed a parsimonious dynamic model to investigate rhythmic control of poly(A) tail length as a process coupled to rhythmic mRNA expression. A global parameter sensitivity analysis of the model reveals that the rhythmicity of poly(A) tail length and mRNA translatability most strongly depend on the rhythmicity of deadenylation -- the process that shortens the poly(A) tail. This effect of rhythmic deadenylation is so strong that deadenylation can potentially synchronize the rhythms of target gene expression. Our findings highlight the critical role of rhythmic deadenylation in the rhythmic control of the mRNA poly(A) tail and gene expression.

 

 

Biophysics and Systems Biology Seminar Series website: http://sites.uci.edu/biophysicsseminar/

 

 

ZOOM Meeting ID: 913 6442 7728 https://uci.zoom.us/j/91364427728