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Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity.

ABSTRACT: Bacterial small RNAs (sRNAs) are critical post-transcriptional regulators that exert broad effects on cell physiology. One class of sRNAs, referred to as trans-acting sRNAs, base-pairs with mRNAs to cause changes in their stability or translation. Another class of sRNAs sequesters RNA-binding proteins that in turn modulate mRNA expression. RNA chaperones play key roles in these regulatory events by promoting base-pairing of sRNAs to mRNAs, increasing the stability of sRNAs, inducing conformational changes on mRNA targets upon binding, or by titrating sRNAs away from their primary targets. In pathogenic bacteria, sRNAs and their chaperones exert broad impacts on both cell physiology and virulence, highlighting the central role of these systems in pathogenesis. This review provides an overview of the growing number and roles of these chaperone proteins in sRNA regulation, highlighting how these proteins contribute to bacterial pathogenesis.

SUBMITTER: Djapgne L

PROVIDER: S-EPMC8311930 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity.

Djapgne Louise L Oglesby Amanda G AG

Frontiers in cellular and infection microbiology 20210712

Bacterial small RNAs (sRNAs) are critical post-transcriptional regulators that exert broad effects on cell physiology. One class of sRNAs, referred to as <i>trans</i>-acting sRNAs, base-pairs with mRNAs to cause changes in their stability or translation. Another class of sRNAs sequesters RNA-binding proteins that in turn modulate mRNA expression. RNA chaperones play key roles in these regulatory events by promoting base-pairing of sRNAs to mRNAs, increasing the stability of sRNAs, inducing confo ...[more]

PMID: 34322396

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Project description:BackgroundWhile eukaryotic noncoding RNAs have recently received intense scrutiny, it is becoming clear that bacterial transcription is at least as pervasive. Bacterial small RNAs and antisense RNAs (sRNAs) are often assumed to be noncoding, due to their lack of long open reading frames (ORFs). However, there are numerous examples of sRNAs encoding for small proteins, whether or not they also have a regulatory role at the RNA level.MethodsHere, we apply flexible machine learning techniques based on sequence features and comparative genomics to quantify the prevalence of sRNA ORFs under natural selection to maintain protein-coding function in 14 phylogenetically diverse bacteria. Importantly, we quantify uncertainty in our predictions, and follow up on them using mass spectrometry proteomics and comparison to datasets including ribosome profiling.ResultsA majority of annotated sRNAs have at least one ORF between 10 and 50 amino acids long, and we conservatively predict that 409±191.7 unannotated sRNA ORFs are under selection to maintain coding (mean estimate and 95% confidence interval), an average of 29 per species considered here. This implies that overall at least 10.3±0.5% of sRNAs have a coding ORF, and in some species around 20% do. 165±69 of these novel coding ORFs have some antisense overlap to annotated ORFs. As experimental validation, many of our predictions are translated in published ribosome profiling data and are identified via mass spectrometry shotgun proteomics. B. subtilis sRNAs with coding ORFs are enriched for high expression in biofilms and confluent growth, and S. pneumoniae sRNAs with coding ORFs are involved in virulence. sRNA coding ORFs are enriched for transmembrane domains and many are predicted novel components of type I toxin/antitoxin systems.ConclusionsWe predict over two dozen new protein-coding genes per bacterial species, but crucially also quantified the uncertainty in this estimate. Our predictions for sRNA coding ORFs, along with predicted novel type I toxins and tools for sorting and visualizing genomic context, are freely available in a user-friendly format at http://disco-bac.web.pasteur.fr. We expect these easily-accessible predictions to be a valuable tool for the study not only of bacterial sRNAs and type I toxin-antitoxin systems, but also of bacterial genetics and genomics.

Dataset Information

Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity.

Publications

Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity.

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