Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown

<p>In the last decade, multiple studies demonstrated that cells maintain a balance of mRNA production and degradation, but the mechanisms by which cells implement this balance remain unknown. Here, we monitored cells&rsquo; total and recently-transcribed mRNA profiles immediately following an acute depletion of Xrn1&mdash;the main 5&prime;-3&prime; mRNA exonuclease&mdash;which was previously implicated in balancing mRNA levels. We captured the detailed dynamics of the&nbsp;adaptation to rapid degradation of Xrn1 and observed a significant accumulation of mRNA, followed by a delayed global reduction in transcription and a gradual return to baseline mRNA levels. We found that this transcriptional response is not unique to Xrn1 depletion; rather, it is induced earlier when upstream factors in the 5&prime;-3&prime; degradation pathway are perturbed. Our data suggest that the mRNA feedback mechanism monitors the accumulation of inputs to the 5&prime;-3&prime; exonucleolytic pathway rather than its outputs.</p>