4.8 Article

Pervasive translation in Mycobacterium tuberculosis

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.73980

Keywords

Mycobacterium tuberculosis; pervasive translation; small protein; sORF; leaderless; None

Categories

Funding

  1. National Institute of Allergy and Infectious Diseases [R21AI117158, R21AI119427]
  2. National Institute of General Medical Sciences [R01GM139277]

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Most bacterial ORFs are identified by automated prediction algorithms, but the algorithms often fail to identify ORFs lacking canonical features. In this study, ribosome profiling is used to identify actively translated ORFs in Mycobacterium tuberculosis. The study reveals the pervasive translation of previously undescribed ORFs, particularly short ones encoding proteins of <= 50 amino acids. The data suggest that the translation of short ORFs in M. tuberculosis serves as a source for evolving new functional proteins.
Most bacterial ORFs are identified by automated prediction algorithms. However, these algorithms often fail to identify ORFs lacking canonical features such as a length of > 50 codons or the presence of an upstream Shine-Dalgarno sequence. Here, we use ribosome profiling approaches to identify actively translated ORFs in Mycobacterium tuberculosis. Most of the ORFs we identify have not been previously described, indicating that the M. tuberculosis transcriptome is pervasively translated. The newly described ORFs are predominantly short, with many encoding proteins of <= 50 amino acids. Codon usage of the newly discovered ORFs suggests that most have not been subject to purifying selection, and hence are unlikely to contribute to cell fitness. Nevertheless, we identify 90 new ORFs (median length of 52 codons) that bear the hallmarks of purifying selection. Thus, our data suggest that pervasive translation of short ORFs in Mycobacterium tuberculosis serves as a rich source for the evolution of new functional proteins.

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