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Diament, A.

Publications and source records attributed to Diament, A..

3 recordsLinked to original sources

Monitoring the translation initiation process in prokaryotes via large-scale examination using optimized SSU-seq technique

Translation initiation is a critical stage of protein synthesis in prokaryotes, where ribosomes assemble on mRNA to begin decoding genetic information. The interactions between ribosomal RNA (rRNA) and mRNA significantly influence this process, with features like ribosomal binding site (RBS) affecting ribosomal dynamics. However, direct experimental validation of these types of interaction is yet to be provided. In this study, we developed an optimized small sub-unit sequencing (SSU-seq) protocol for Escherichia coli, enabling the detailed examination of ribosomal complexes and subunits dynamics. Unlike Ribo-seq, which primarily maps fully assembled ribosomes, SSU-seq captures both ribosomal subunits and intact ribosomes, offering a comprehensive view of translation initiation and elongation events. By integrating experimental data with predictive models, our study advances the understanding of translation regulation in prokaryotes and underscores the utility of SSU-seq in decoding the complexities of ribosome-mRNA interactions. Our analysis reveals distinct patterns of small subunit distribution across the entire mRNAs with higher density near positions with stronger rRNA-mRNA hybridization. The results may suggest that rRNA-mRNA hybridization positions along the entire transcript facilitate efficient start codon recognition by maintaining proximity between the small subunit and the mRNA.

systems biology↗

Comprehensive Survey of Gut Microbiome Associations with Health Conditions in the Human Phenotype Project

The human gut microbiome is increasingly implicated with diverse health conditions, highlighting the importance of developing comprehensive resources to systematically map these associations. In this study, we leveraged the Human Phenotype Project (HPP) 10K cohort, a large, deeply phenotyped population study cohort with extensive metagenomic profiling, to explore associations between the gut microbiome and 37 health indications. These include conditions with established or emerging links to the microbiome, such as obesity, diabetes, hyperlipidemia, metabolic syndrome, inflammation, liver disease, cardiovascular and kidney conditions, immune and allergic diseases, gastrointestinal symptoms, mental health, and sleep-related traits. Using a curated set of approximately 200 refined phenotypic features and analyzing 1,184 microbial species, we performed robust statistical association analyses. We observed significant enrichment of associations in 14 health indications, with most associations reflecting increased microbial abundance in favorable health states, thereby suggesting potential microbial targets for intervention. This work introduces a publicly available, high-resolution resource to facilitate future research and support the development of microbiome-informed health strategies.

genomics↗

Prokaryotic rRNA-mRNA interactions are involved in all translation steps and shape bacterial transcripts

The well-established Shine-Dalgarno model suggests that translation initiation in bacteria is regulated via base-pairing between ribosomal RNA (rRNA) and mRNA. However, little is currently known about the contribution of such interactions to the rest of the translation process and to the way bacterial transcript evolve. We used novel computational analyses and modelling of 823 bacterial genomes coupled with experiments to demonstrate that rRNA-mRNA interactions are diverse and regulate not only initiation, but all translation steps from pre-initiation to termination across the many bacterial phyla that have the Shine-Dalgarno sequence. As these interactions dictate translation efficiency, they serve as a driving evolutionary force for shaping transcripts in bacteria. We observed selection for strong rRNA-mRNA interactions in regions where such interactions are likely to enhance initiation, regulate early elongation and ensure the fidelity of translation termination. We discovered selection against strong interactions and for intermediate interactions in coding regions and present evidence that these interactions maximize elongation efficiency while also enhancing initiation by guiding free ribosomal units to the start codon. ImportancePrevious research has reported the significant influence of rRNA-mRNA interactions mainly in the initiation phase of translation. The results reported in this paper suggest that, in addition to the rRNA-mRNA interactions near the start codon that trigger initiation in bacteria, rRNA-mRNA interactions affect all sub-stages of the translation process (pre-initiation, initiation, elongation, termination). In addition, these interactions affect the way evolutionary forces shape the bacterial transcripts while considering trade-offs between the effects of different interactions across different transcript regions on translation efficacy and efficiency. Due to the centrality of the translation process, these findings are relevant to all biomedical disciplines.

systems biology↗