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Multiples mécanismes de régulation post-transcriptionnelle chez les bactéries : des structures d’ARN messager aux ARN régulateurs

Abstract : In order to perfectly adapt to their environment, bacteria require a tight gene expression regulation. This can occur through post-transcriptional control by numerous regulatory RNAs (or small RNAs, sRNAs). These sRNAs can target mRNAs, leading to a fast regulation of protein synthesis. Most often, sRNAs base-pair with their target mRNAs at the ribosome binding site (RBS), therefore competing with the ribosome for the binding with the mRNA and repressing gene expression. However, many other regulatory mechanisms involve sRNAs. We have demonstrated that the two sRNAs OmrA and OmrB, conserved among enterobacteria, repress the synthesis of the FepA receptor for iron-enterobactin complexes through base-pairing with a secondary structure within fepA mRNA. This stem-loop structure is located downstream of fepA RBS, and most surprisingly, promotes 30S ribosomal subunit binding to fepA mRNA, therefore activating FepA synthesis. Similar stem-loop structures have been predicted in other mRNAs, such as the bamA mRNA encoding the essential subunit of the Bam outer membrane protein assembly complex. As for fepA mRNA, the stem-loop found in bamA mRNA also promotes ribosome binding, showing that this regulatory mechanism could be widespread considering the strong conservation of bamA among Gram negative bacteria. Moreover, these results challenge the commonly admitted view of mRNA secondary structures being repressors of gene expression. Two other sRNAs also repress fepA expression in an OmrA/B-independent fashion, namely SdsR and RseX. For each of these sRNAs, the regulatory mechanism involved is different. Indeed, SdsR most likely acts through two distinct binding sites, one of which leading to a classical competition with the ribosome binding. Meanwhile, RseX repression requires most of fepA 5’UTR, including sequences at about 100nt upstream of the start codon. Finally, each of these sRNAs is expressed upon diverse stimuli, considerably extending our knowledge of the signals leading to fepA regulation, for which only the Fur-dependent derepression upon iron starvation was known. This work highlights the great versatility of regulatory mechanisms involving RNAs. This illustrates how RNAs structural flexibility and sequence diversity is a key source of diversity for evolution
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Submitted on : Friday, February 1, 2019 - 12:55:35 PM
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Jonathan Jagodnik. Multiples mécanismes de régulation post-transcriptionnelle chez les bactéries : des structures d’ARN messager aux ARN régulateurs. Microbiologie et Parasitologie. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCC111⟩. ⟨tel-02000219⟩



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