Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

The molecular machinery of RNA metabolism and riboregulation in bacteria

In plain English

AI plain-English summary

Bacteria produce dozens of small RNA molecules to rewire their gene activity when under stress, and this project will capture the first detailed snapshots of the molecular machines that process and destroy those RNAs. Current antibiotics mostly target bacterial growth, but many chronic infections involve bacteria that have switched into a slow-growing, stress-resistant state. The molecular machinery that controls RNA-based gene regulation is a potential new target for drugs that could disable bacteria in this persistent state. The researchers will use structural biology to visualise how the degradative enzyme complex captures RNA transcripts, feeds them into its active site, and either chops them up or trims them into mature forms. They will also map which RNA targets the chaperone proteins and the degradation machinery bind to, and test whether those targets shift during the cell cycle or under different physiological conditions. This is fundamental science. It asks how even simple bacteria achieve complex, rapid responses to their environment using RNA-based regulation. A deeper understanding of these molecular mechanisms could eventually inform the design of novel antimicrobials that disrupt bacterial stress responses rather than growth itself—an approach that might slow the development of resistance.

View original technical description
In response to stress conditions and environmental changes, bacteria generate scores of small RNAs that play key roles in reshaping the dynamic landscape of gene expression. This process involves chaperone proteins that facilitate the actions of such regulatory RNAs and enzymes that affect transcript lifetimes. We aim to understand the molecular basis of these processes. Trapped intermediates of the degradative machinery with bound regulatory RNAs and targeted substrates will be structurally characterised to visualize how transcripts are captured and channelled to active sites, where they meet a fate of rapid degradation or processing into matured forms. We will identify RNA targets of chaperones and the degradative machinery and explore whether the patterns change with physiological state or during the cell cycle, and why. We want to understand why the degradative machinery has a sub-cellular localization and the origins of its dynamic and cooperative interactions with substrates and the translational machinery. Our studies will help to explain how the use of RNA enables speed and accuracy to be attained in genetic regulation and enriches the capacity of even the simplest organisms to exhibit complex behaviour in homeostasis, development and pathogenesis. This knowledge could be exploited to treat threatening bacterial infections.

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Researchers

Bonaventura LUISI (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Decoding riboregulation in complex cellular behaviour of bacteria
Organisation and regulation of bacterial enhancer-binding proteins
RNA processing and degradation
Regulation of elongation by RNA polymerase and ribosome via intrinsic signals and transcription-translation coupling
Regulated transcript stability

Original classification

Investigator Award in Science

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