Gene recoding by synonymous mutations creates promiscuous intragenic transcription initiation in mycobacteria

• Published in: mBio Vol. 14; no. 5; p. e0084123
• Main Authors: Hegelmeyer, Nuri K, Parkin, Lia A, Previti, Mary L, Andrade, Joshua, Utama, Raditya, Sejour, Richard J, Gardin, Justin, Muller, Stephanie, Ketchum, Steven, Yurovsky, Alisa, Futcher, Bruce, Goodwin, Sara, Ueberheide, Beatrix, Seeliger, Jessica C
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 31.10.2023
• Subjects: Codon; codon pair bias; Genetics and Molecular Biology; Mycobacterium; Mycobacterium - genetics; recoding; Research Article; RNA, Messenger; Silent Mutation; transcription; translation; tuberculosis; translation; Mycobacterium; codon pair bias; recoding; transcription; tuberculosis
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.00841-23

( ) is the causative agent of tuberculosis, one of the deadliest infectious diseases worldwide. Previous studies have established that synonymous recoding to introduce rare codon pairings can attenuate viral pathogens. We hypothesized that non-optimal codon pairing could be an effective strategy for attenuating gene expression to create a live vaccine for . We instead discovered that these synonymous changes enabled the transcription of functional mRNA that initiated in the middle of the open reading frame and from which many smaller protein products were expressed. To our knowledge, this is one of the first reports that synonymous recoding of a gene in any organism can create or induce intragenic transcription start sites.