دورية أكاديمية
أعرض في EDS

A novel regulatory interplay between atypical B12 riboswitches and uORF translation in Mycobacterium tuberculosis.

التفاصيل البيبلوغرافية
العنوان: A novel regulatory interplay between atypical B12 riboswitches and uORF translation in Mycobacterium tuberculosis.
المؤلفون: Kipkorir T; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK., Polgar P; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK., Barker D; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK., D'Halluin A; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK., Patel Z; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK., Arnvig KB; Institute for Structural and Molecular Biology, University College London, Gower Street, WC1E 6BT London, UK.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Jul 22; Vol. 52 (13), pp. 7876-7892.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Riboswitch*/genetics , Mycobacterium tuberculosis*/genetics , Mycobacterium tuberculosis*/metabolism , Gene Expression Regulation, Bacterial* , Protein Biosynthesis*/genetics , Open Reading Frames*/genetics , Vitamin B 12*/metabolism, Nucleic Acid Conformation ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Ligands ; Base Sequence ; RNA, Bacterial/metabolism ; RNA, Bacterial/genetics
مستخلص: Vitamin B12 is an essential cofactor in all domains of life and B12-sensing riboswitches are some of the most widely distributed riboswitches. Mycobacterium tuberculosis, the causative agent of tuberculosis, harbours two B12-sensing riboswitches. One controls expression of metE, encoding a B12-independent methionine synthase, the other controls expression of ppe2 of uncertain function. Here, we analysed ligand sensing, secondary structure and gene expression control of the metE and ppe2 riboswitches. Our results provide the first evidence of B12 binding by these riboswitches and show that they exhibit different preferences for individual isoforms of B12, use distinct regulatory and structural elements and act as translational OFF switches. Based on our results, we propose that the ppe2 switch represents a new variant of Class IIb B12-sensing riboswitches. Moreover, we have identified short translated open reading frames (uORFs) upstream of metE and ppe2, which modulate the expression of their downstream genes. Translation of the metE uORF suppresses MetE expression, while translation of the ppe2 uORF is essential for PPE2 expression. Our findings reveal an unexpected regulatory interplay between B12-sensing riboswitches and the translational machinery, highlighting a new level of cis-regulatory complexity in M. tuberculosis. Attention to such mechanisms will be critical in designing next-level intervention strategies.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: MR/S009647/1 UK Medical Research Council; NIF\R1\180833 Newton International Fellowship; 204841/Z/16/Z Wellcome Institutional Strategic Support Fund; 225605/Z/22/Z Wellcome Early Career Award; United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Riboswitch)
P6YC3EG204 (Vitamin B 12)
0 (Bacterial Proteins)
0 (Ligands)
0 (RNA, Bacterial)
تواريخ الأحداث: Date Created: 20240506 Date Completed: 20240721 Latest Revision: 20240723
رمز التحديث: 20240723
مُعرف محوري في PubMed: PMC11260477
DOI: 10.1093/nar/gkae338
PMID: 38709884
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae338