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Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape


The current paradigm for bacterial translation is based on an mRNA that includes an untranslated leader sequence containing the ribosome-binding site upstream of the initiation codon. We applied genome-scale approaches to map the protein-coding regions in the genomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We found that nearly one-quarter of mycobacterial transcripts are leaderless in mycobacterial species, thus indicating that ribosomes must recognize these mRNAs by a novel mechanism and suggesting that there are alternative modes of bacterial translation beyond the Escherichia coli paradigm. Our translational profiling showed that many mycobacterial proteins are mis-annotated, and also found many new genes encoding small proteins that had been previously overlooked, which are likely to play novel roles in diverse cellular processes. We also developed a new reporter system that provides mechanistic insights into translation initiation through deep sequencing. Our data show that leaderless translation is a robust process that is conserved in mycobacteria, that leaderless translation only requires that the mRNA begin with a start codon, and predict that mycobacteria encode hundreds of small proteins. This work will help us understand gene structure, genome organization and protein expression in bacteria, and how the translational machinery differs in different organisms.


Vyšlo v časopise: Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005641
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005641

Souhrn

The current paradigm for bacterial translation is based on an mRNA that includes an untranslated leader sequence containing the ribosome-binding site upstream of the initiation codon. We applied genome-scale approaches to map the protein-coding regions in the genomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We found that nearly one-quarter of mycobacterial transcripts are leaderless in mycobacterial species, thus indicating that ribosomes must recognize these mRNAs by a novel mechanism and suggesting that there are alternative modes of bacterial translation beyond the Escherichia coli paradigm. Our translational profiling showed that many mycobacterial proteins are mis-annotated, and also found many new genes encoding small proteins that had been previously overlooked, which are likely to play novel roles in diverse cellular processes. We also developed a new reporter system that provides mechanistic insights into translation initiation through deep sequencing. Our data show that leaderless translation is a robust process that is conserved in mycobacteria, that leaderless translation only requires that the mRNA begin with a start codon, and predict that mycobacteria encode hundreds of small proteins. This work will help us understand gene structure, genome organization and protein expression in bacteria, and how the translational machinery differs in different organisms.


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