Work

MazF endoribonuclease promotes resolution of transcription–replication conflicts at ribosomal RNA genes in Escherichia coli

Year: 2025

Type: article

Abstract: Toxins from toxin-antitoxin (TA) systems, widely distributed genetic elements in prokaryotic genomes, are traditionally viewed as growth inhibitors. This study challenges this view by uncovering a growth-promoting function for MazF, the toxin component of the Escherichia coli MazF/MazE TA system. MazF is a sequence-specific endoribonuclease that cleaves single-stranded RNA, including ribosomal RNA (rRNA) precursors. While ectopic overexpression of MazF causes growth arrest, we show here that, when expressed at its native expression levels, it alleviates both co-directional and head-on transcription-replication conflicts at highly transcribed rRNA operons. By resolving these conflicts, MazF mitigates DNA damage, reduces cell mortality, and ultimately facilitates growth resumption. This function is particularly critical during the exit from stationary phase, when the rRNA copy operon number is low or when ribosome integrity is compromised. We further demonstrate that MazF is active, indicating its release from MazE antitoxin control, during regrowth from stationary phase, heat shock at 50°C, and colistin treatment. Together, these findings reveal an unrecognized role of TA systems in promoting cellular resilience, maintaining genome stability, and enabling recovery from stress, thereby providing new insights into their complex biological functions.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1034

Authors: Sebastien Fleurier, Ivan Matic

Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Cité, Institut Cochin

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funder: Agence Nationale de la Recherche