A tRNA modifying enzyme as a tunable regulatory nexus for bacterial stress responses and virulence.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
22 07 2022
Historique:
accepted: 08 02 2022
revised: 02 02 2022
received: 26 05 2021
pubmed: 26 2 2022
medline: 26 7 2022
entrez: 25 2 2022
Statut: ppublish

Résumé

Post-transcriptional modifications can impact the stability and functionality of many different classes of RNA molecules and are an especially important aspect of tRNA regulation. It is hypothesized that cells can orchestrate rapid responses to changing environmental conditions by adjusting the specific types and levels of tRNA modifications. We uncovered strong evidence in support of this tRNA global regulation hypothesis by examining effects of the well-conserved tRNA modifying enzyme MiaA in extraintestinal pathogenic Escherichia coli (ExPEC), a major cause of urinary tract and bloodstream infections. MiaA mediates the prenylation of adenosine-37 within tRNAs that decode UNN codons, and we found it to be crucial to the fitness and virulence of ExPEC. MiaA levels shifted in response to stress via a post-transcriptional mechanism, resulting in marked changes in the amounts of fully modified MiaA substrates. Both ablation and forced overproduction of MiaA stimulated translational frameshifting and profoundly altered the ExPEC proteome, with variable effects attributable to UNN content, changes in the catalytic activity of MiaA, or availability of metabolic precursors. Cumulatively, these data indicate that balanced input from MiaA is critical for optimizing cellular responses, with MiaA acting much like a rheostat that can be used to realign global protein expression patterns.

Identifiants

pubmed: 35212379
pii: 6536892
doi: 10.1093/nar/gkac116
pmc: PMC9303304
doi:

Substances chimiques

Codon 0
RNA, Transfer 9014-25-9
Alkyl and Aryl Transferases EC 2.5.-
adenylate isopentenyltransferase EC 2.5.1.27

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7570-7590

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM126956
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095647
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM134331
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135918
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055434
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007115
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI088086
Pays : United States

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Brittany A Fleming (BA)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Matthew G Blango (MG)

Junior Research Group RNA Biology of Fungal Infections, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI), 07745 Jena, Germany.

Alexis A Rousek (AA)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

William M Kincannon (WM)

Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.

Alexander Tran (A)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Adam J Lewis (AJ)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Colin W Russell (CW)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Qin Zhou (Q)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Lisa M Baird (LM)

Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.

Amelia E Barber (AE)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

John R Brannon (JR)

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Connor J Beebout (CJ)

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Vahe Bandarian (V)

Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.

Maria Hadjifrangiskou (M)

Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Michael T Howard (MT)

Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.

Matthew A Mulvey (MA)

Division of Microbiology and Immunology, Pathology Department, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

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