Abstract
In the last decade, multiple studies have shown that cells maintain a balance of mRNA production and degradation in different settings, but the mechanisms by which cells implement this balance remain poorly understood. Here, we monitored cells’ mRNA and nascent mRNA profiles immediately following an acute depletion of Xrn1 - the main 5’-3’ mRNA exonuclease - that was previously implicated in balancing mRNA levels. We captured the detailed dynamics of the cells’ adaptation to rapid degradation of Xrn1 and observed a significant accumulation of mRNA, followed by global reduction in nascent transcription and a return to baseline mRNA levels. We present evidence that this transcriptional response is linked to cell cycle progression, and that it is not unique to Xrn1 depletion; rather, it is induced earlier when upstream factors in the 5’-3’ degradation pathway are perturbed. Using the detailed dynamic measurements we hypothesize a cell-cycle-linked feedback mechanism that monitors the accumulation of inputs to the 5’-3’ exonucleolytic pathway rather than its outputs.
Competing Interest Statement
The authors have declared no competing interest.