Microbial metabolites shape mammalian protein translation

Area of Science:

• Molecular Biology
• Microbiology
• Cell Biology

Background:

• Eukaryotic queuosine modification in transfer RNA (tRNA) is crucial for cellular function.
• This modification relies on the uptake of the molecule queuine, primarily derived from microbial sources.
• The precise mechanisms by which microbial metabolites influence host cell processes are an active area of research.

Purpose of the Study:

• To investigate the role of bacterial queuine biosynthesis intermediates in mammalian cells.
• To elucidate the interaction between pre-queuosine 1 (preQ1) and host cell targets involved in tRNA modification.
• To understand how this interaction impacts fundamental cellular processes like protein translation and proliferation.

Main Methods:

• Utilized biochemical assays to study the binding interactions between preQ1, queuine, and mammalian tRNA.
• Employed cell-based assays to monitor protein translation rates and cell proliferation under varying conditions.
• Analyzed the effects of preQ1 and queuine on specific tRNA modification pathways.

Main Results:

• Demonstrated that pre-queuosine 1 (preQ1), a bacterial queuine biosynthesis intermediate, directly competes with queuine for binding to mammalian tRNA targets.
• Showed that this competition antagonistically modulates protein translation efficiency.
• Observed that preQ1 influences mammalian cell proliferation, suggesting a significant impact on host cell physiology.

Conclusions:

• Pre-queuosine 1 (preQ1) acts as a key microbial metabolite that can interfere with host cell tRNA modification.
• The competition between preQ1 and queuine highlights a novel mechanism of host-microbe interaction impacting protein synthesis and cell growth.
• This finding has implications for understanding the broader influence of the gut microbiome on host cell function and organismal health.