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

Journal Article · · RNA
 [1];  [1];  [1];  [1];  [1]
  1. Emory Univ., Atlanta, GA (United States)
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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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
NE-CAT ID24-E; 5T32GM8367; GM093278; 0953714
OSTI ID:
1274774
Journal Information:
RNA, Vol. 22, Issue 8; ISSN 1355-8382
Publisher:
Cambridge University PressCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 9 works
Citation information provided by
Web of Science

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Cited By (4)

Monomeric YoeB toxin retains RNase activity but adopts an obligate dimeric form for thermal stability journal September 2019
Translation-dependent mRNA cleavage by YhaV in Escherichia coli journal June 2017
HigB of Pseudomonas aeruginosa Enhances Killing of Phagocytes by Up-Regulating the Type III Secretion System in Ciprofloxacin Induced Persister Cells journal October 2016
Structural basis of transcriptional regulation by the HigA antitoxin journal April 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
toxin–antitoxin modules
stringent response
RNase
ribosome
protein synthesis
mRNA