Transcription feedback dynamics in the wake of cytoplasmic degradation shutdown

Purpose: Studying the dynamics of the transcriptional response to acute depletion of various critical mRNA processing factors Methods: We used 4tU labeling and high-throughput polyA RNA-seq in yeast following auxin inducible degradation of key proteins. Results: We captured the detailed dynamics of cells' adaptation to rapid degradation of Xrn1 and observed a significant accumulation of mRNA, followed by a delayed global reduction in nascent transcription and a gradual 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. Conclusions: Our data suggest that the RNA feedback mechanism is cell-cycle-linked and monitors the accumulation of inputs to the 5'-3' exonucleolytic pathway rather than its outputs. Overall design: Most samples are 4tU-labeled RNA-seq following the depletion of a key protein from cells.