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

The circadian rhythm in 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 suggest 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 poly(A) tail oscillate over the day. Here we constructed a parsimonious model to investigate rhythmic control of poly(A) tail length as a coupled process to rhythmic mRNA expression. A global parameter sensitivity analysis on 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 impact is so strong that deadenylation can potentially 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.