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Title: mRNA bound to the 30S subunit is a HigB toxin substrate

Abstract

Activation of bacterial toxins during stress results in cleavage of mRNAs in the context of the ribosome. These toxins are thought to function as global translational inhibitors yet recent studies suggest each may have distinct mRNA specificities that result in selective translation for bacterial survival. Here we demonstrate that mRNA in the context of a bacterial 30S subunit is sufficient for ribosome-dependent toxin HigB endonucleolytic activity, suggesting that HigB interferes with the initiation step of translation. We determined the X-ray crystal structure of HigB bound to the 30S, revealing that two solvent-exposed clusters of HigB basic residues directly interact with 30S 16S rRNA helices 18, 30, and 31. We further show that these HigB residues are essential for ribosome recognition and function. Comparison with other ribosome-dependent toxins RelE and YoeB reveals that each interacts with similar features of the 30S aminoacyl (A) site yet does so through presentation of diverse structural motifs.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. Emory Univ., Atlanta, GA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1274774
Grant/Contract Number:  
NE-CAT ID24-E; 5T32GM8367; GM093278; 0953714
Resource Type:
Accepted Manuscript
Journal Name:
RNA
Additional Journal Information:
Journal Volume: 22; Journal Issue: 8; Journal ID: ISSN 1355-8382
Publisher:
Cambridge University Press
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; toxin–antitoxin modules; stringent response; RNase; ribosome; protein synthesis; mRNA

Citation Formats

Schureck, Marc A., Maehigashi, Tatsuya, Miles, Stacey J., Marquez, Jhomar, and Dunham, Christine M. mRNA bound to the 30S subunit is a HigB toxin substrate. United States: N. p., 2016. Web. doi:10.1261/rna.056218.116.
Schureck, Marc A., Maehigashi, Tatsuya, Miles, Stacey J., Marquez, Jhomar, & Dunham, Christine M. mRNA bound to the 30S subunit is a HigB toxin substrate. United States. https://doi.org/10.1261/rna.056218.116
Schureck, Marc A., Maehigashi, Tatsuya, Miles, Stacey J., Marquez, Jhomar, and Dunham, Christine M. Wed . "mRNA bound to the 30S subunit is a HigB toxin substrate". United States. https://doi.org/10.1261/rna.056218.116. https://www.osti.gov/servlets/purl/1274774.
@article{osti_1274774,
title = {mRNA bound to the 30S subunit is a HigB toxin substrate},
author = {Schureck, Marc A. and Maehigashi, Tatsuya and Miles, Stacey J. and Marquez, Jhomar and Dunham, Christine M.},
abstractNote = {Activation of bacterial toxins during stress results in cleavage of mRNAs in the context of the ribosome. These toxins are thought to function as global translational inhibitors yet recent studies suggest each may have distinct mRNA specificities that result in selective translation for bacterial survival. Here we demonstrate that mRNA in the context of a bacterial 30S subunit is sufficient for ribosome-dependent toxin HigB endonucleolytic activity, suggesting that HigB interferes with the initiation step of translation. We determined the X-ray crystal structure of HigB bound to the 30S, revealing that two solvent-exposed clusters of HigB basic residues directly interact with 30S 16S rRNA helices 18, 30, and 31. We further show that these HigB residues are essential for ribosome recognition and function. Comparison with other ribosome-dependent toxins RelE and YoeB reveals that each interacts with similar features of the 30S aminoacyl (A) site yet does so through presentation of diverse structural motifs.},
doi = {10.1261/rna.056218.116},
journal = {RNA},
number = 8,
volume = 22,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}

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Cited by: 9 works
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