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Our Publications

Nature, 2024

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage. Here, we describe Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter urativorans. Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon–EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues in Mycobacteria bind to ribosomes in a similar fashion. 

Annual Reviews Virology, 2023

A comprehensive review covering the structural and mechanistic basis of programmed -1 ribosomal frameshifting (-1PRF) in RNA viruses. Here we provide a summary of historical perspectives, highlight recent advances and discuss to what extent a general model for −1PRF remains a useful way of thinking.

Insights from structural studies of the cardiovirus 2A protein

BioScience Reports, 2022

A short review summarising what we've learned from our recent structures of cardiovirus 2A proteins from encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelitis virus (TMEV).

Structural and molecular basis for cardiovirus 2A protein as a viral gene expression switch

Nature Communications, 2021

Cardioviruses need the 2A protein to activate ribosomal frameshifting during infection. Here we present the crystal structure of 2A from EMCV, revealing a new RNA-binding fold. We then investigate how 2A binds to a structured RNA element in the viral genome that regulates frameshifting. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, increasing the force required to unwind it - likely explaining its mechanism of action. Finally, using cryo-EM we characterise a direct interaction between 2A and ribosomal RNA.

Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus

Nucleic Acids Research, 2021

The 2A protein TMEV acts as a switch to stimulate frameshifting during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of 2A-induced ribosomal pauses and present evidence of ribosome queueing at frameshifting signal.  

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