Targeting Recoding by <i>trans</i>-Translation to Develop Antibiotics

<i>trans</i>-Translation is a recoding event in which a translating ribosome switches from the engaged messenger RNA (mRNA) to a specialized reading frame within transfer-messenger RNA (tmRNA) without releasing the nascent polypeptide, producing a protein that is encoded in two physically distinct RNA molecules. <i>trans</i>-Translation is the most abundant form of recoding and is found throughout the bacterial kingdom. In <i>Escherichia coli</i> growing in liquid culture, ∼5% of newly synthesized proteins are recoded through <i>trans</i>-translation. The importance of this pathway for pathogenic bacteria makes it a potential target for antibiotic development. This review covers the role of <i>trans</i>-translation in pathogenesis, potential points for inhibition, and the progress in developing <i>trans</i>-translation inhibitors as antibiotics.

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Publication Details

Journal
Cold Spring Harbor Perspectives in Biology
Published
2025-09-22
DOI
https://doi.org/10.1101/cshperspect.a041864
Primary Topic
RNA and protein synthesis mechanisms
Type
article
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article

Targeting Recoding by trans-Translation to Develop Antibiotics

C.M. Dunham, Kenneth C. Keiler, Akanksha Varshney
Cold Spring Harbor Perspectives in Biology
RNA and protein synthesis mechanisms
article

Targeting Recoding by trans-Translation to Develop Antibiotics

C.M. Dunham, Kenneth C. Keiler, Akanksha Varshney
article en

Abstract

<i>trans</i>-Translation is a recoding event in which a translating ribosome switches from the engaged messenger RNA (mRNA) to a specialized reading frame within transfer-messenger RNA (tmRNA) without releasing the nascent polypeptide, producing a protein that is encoded in two physically distinct RNA molecules. <i>trans</i>-Translation is the most abundant form of recoding and is found throughout the bacterial kingdom. In <i>Escherichia coli</i> growing in liquid culture, ∼5% of newly synthesized proteins are recoded through <i>trans</i>-translation. The importance of this pathway for pathogenic bacteria makes it a potential target for antibiotic development. This review covers the role of <i>trans</i>-translation in pathogenesis, potential points for inhibition, and the progress in developing <i>trans</i>-translation inhibitors as antibiotics.

Cold Spring Harbor Perspectives in Biology
Emory University (US), The University of Texas at Austin (US)
RNA and protein synthesis mechanisms
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