Microbiome activity revealed in unprecedented detail by tRNA sequencing.

The microbiota is a diverse bacterial microorganism living in and on all mammals whose metabolic product provides balance, immunity and, in some cases, disease to the host’s body.  Therefore, it is crucial to measure the cause, levels and moment of production of these microbial metabolites, however, no system sensitive enough has been developed to measure transfer ribonucleic acid (tRNA), a type of RNA molecule known to assist in the decoding of messenger RNA into proteins such as metabolites.  Now, a study from researchers at the University of Chicago develops a new technique to directly analyze tRNA, providing a clearer picture of microbial community responses to environmental changes, such as varying temperatures or diet.  The team states developing a clear picture of tRNA dynamics will allow the global medical community to understand the activity of naturally occurring microbiomes and their metabolites.  The opensource study is published in the journal Nature Communications.

Previous studies show high-throughput sequencing of ribosomal RNA, gene amplicons and shotgun metagenomes enabled extensive culture-independent characterizations of microbial diversity, however, these approaches are not suitable to gain insights into the physiology of microbial populations and their extensive metabolic repertoire.  The current study demonstrates the application of tRNA sequencing to gut microbiome samples from mice fed either a low-fat or high-fat diet.

The current study uses novel software to compile a catalog of tRNA molecules recovered from cecal samples of mice, tracing them back to the specific bacteria responsible for their expression and measures chemical modifications in tRNA.  Results show the analysis of gut samples using tRNA-seq distinguishes high-fat and low-fat-fed mice and reveals diet-dependent variations in tRNA modifications.  Data findings show the analysis provides taxon-specific in situ insights into the dynamics of tRNA gene expression and post-transcriptional modifications within complex environmental microbiomes, providing scientific specificity.

The lab explains each tRNA in bacteria has an average of eight chemical modifications used to tune its function, their new tRNA-seq and analysis strategy detects two of them, and can also measure the amount of modification on a scale from 0 to 100% at each site. They go on to add the level of one of the modifications, called m1A, was observed to be higher in the gut microbiome of mice fed a high-fat diet.

The team surmises they have developed a system to record modification level change in tRNA in any microbiome in unprecedented detail.  For the future, the researchers state by providing quick and affordable insights into the core of protein synthesis and translation, tRNA sequencing may provide insights into microbial responses to subtle environmental changes.

Source: University of Chicago

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