Transcription feedback dynamics in the wake of cytoplasmic mRNA degradation shutdown

Alon Chappleboim, Daphna Joseph-Strauss, Omer Gershon, Nir Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageAmerican English
Pages (from-to)5864-5880
Number of pages17
JournalNucleic Acids Research
Volume50
Issue number10
DOIs
StatePublished - 10 Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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