Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown

• Autores: Alon Chappleboim, Daphna Joseph-Strauss, Omer Gershon, Nir Friedman
• Localización: Nucleic acids research, ISSN 0305-1048, Vol. 50, Nº. 10, 2022, págs. 5864-5880
• Idioma: inglés
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• Resumen

  • 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.