Reference: Chappleboim A, et al. (2022) Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown. Nucleic Acids Res 50(10):5864-5880

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Abstract


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' total and recently-transcribed mRNA profiles immediately following an acute depletion of Xrn1-the main 5'-3' mRNA exonuclease-which was previously implicated in balancing mRNA levels. We captured the detailed dynamics of the 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'-3' degradation pathway are perturbed. Our data suggest that the mRNA feedback mechanism monitors the accumulation of inputs to the 5'-3' exonucleolytic pathway rather than its outputs.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Chappleboim A, Joseph-Strauss D, Gershon O, Friedman N
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