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      An overview of gene regulation in bacteria by small RNAs derived from mRNA 3′ ends

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          Abstract

          Over the past two decades, small noncoding RNAs (sRNAs) that regulate mRNAs by short base pairing have gone from a curiosity to a major class of post-transcriptional regulators in bacteria. They are integral to many stress responses and regulatory circuits, affecting almost all aspects of bacterial life. Following pioneering sRNA searches in the early 2000s, the field quickly focused on conserved sRNA genes in the intergenic regions of bacterial chromosomes. Yet, it soon emerged that there might be another rich source of bacterial sRNAs—processed 3′ end fragments of mRNAs. Several such 3′ end-derived sRNAs have now been characterized, often revealing unexpected, conserved functions in diverse cellular processes. Here, we review our current knowledge of these 3′ end-derived sRNAs—their biogenesis through ribonucleases, their molecular mechanisms, their interactions with RNA-binding proteins such as Hfq or ProQ and their functional scope, which ranges from acting as specialized regulators of single metabolic genes to constituting entire noncoding arms in global stress responses. Recent global RNA interactome studies suggest that the importance of functional 3′ end-derived sRNAs has been vastly underestimated and that this type of cross-regulation between genes at the mRNA level is more pervasive in bacteria than currently appreciated.

          Abstract

          There are a growing number of examples of bacterial mRNAs that produce small RNAs cleaved from their own 3′ ends to post-transcriptionally control other genes.

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          Most cited references142

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          The multilayered complexity of ceRNA crosstalk and competition.

          Recent reports have described an intricate interplay among diverse RNA species, including protein-coding messenger RNAs and non-coding RNAs such as long non-coding RNAs, pseudogenes and circular RNAs. These RNA transcripts act as competing endogenous RNAs (ceRNAs) or natural microRNA sponges - they communicate with and co-regulate each other by competing for binding to shared microRNAs, a family of small non-coding RNAs that are important post-transcriptional regulators of gene expression. Understanding this novel RNA crosstalk will lead to significant insight into gene regulatory networks and have implications in human development and disease.
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            Quantifying absolute protein synthesis rates reveals principles underlying allocation of cellular resources.

            Quantitative views of cellular functions require precise measures of rates of biomolecule production, especially proteins-the direct effectors of biological processes. Here, we present a genome-wide approach, based on ribosome profiling, for measuring absolute protein synthesis rates. The resultant E. coli data set transforms our understanding of the extent to which protein synthesis is precisely controlled to optimize function and efficiency. Members of multiprotein complexes are made in precise proportion to their stoichiometry, whereas components of functional modules are produced differentially according to their hierarchical role. Estimates of absolute protein abundance also reveal principles for optimizing design. These include how the level of different types of transcription factors is optimized for rapid response and how a metabolic pathway (methionine biosynthesis) balances production cost with activity requirements. Our studies reveal how general principles, important both for understanding natural systems and for synthesizing new ones, emerge from quantitative analyses of protein synthesis. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria.

              Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibiotic-responsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands.
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                Author and article information

                Contributors
                Journal
                FEMS Microbiol Rev
                FEMS Microbiol Rev
                femsre
                FEMS Microbiology Reviews
                Oxford University Press
                0168-6445
                1574-6976
                September 2022
                07 April 2022
                07 April 2022
                : 46
                : 5
                : fuac017
                Affiliations
                Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI) , D-97080 Würzburg, Germany
                Institute for Molecular Infection Biology, University of Würzburg , D-97080 Würzburg, Germany
                Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI) , D-97080 Würzburg, Germany
                Institute for Molecular Infection Biology, University of Würzburg , D-97080 Würzburg, Germany
                Author notes
                Corresponding author: Josef-Schneider-Str. 2 / D15, D-97080 Würzburg, Germany. Tel: +49-931-3182575; Fax: +49-931-3182578; E-mail: joerg.vogel@ 123456uni-wuerzburg.de

                Present address: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.

                Author information
                https://orcid.org/0000-0002-2144-0545
                https://orcid.org/0000-0003-3052-4430
                Article
                fuac017
                10.1093/femsre/fuac017
                9438474
                35388892
                d711c406-96a3-42e5-8683-6e1db81feea8
                © The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 October 2021
                : 30 March 2022
                : 05 April 2022
                Page count
                Pages: 19
                Funding
                Funded by: DFG, DOI 10.13039/501100001659;
                Award ID: Vo875‐18
                Categories
                Review Article
                AcademicSubjects/SCI01150

                Microbiology & Virology
                3′ utr,srna,post-transcriptional control,regulatory networks,bacteria
                Microbiology & Virology
                3′ utr, srna, post-transcriptional control, regulatory networks, bacteria

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