Mycobacteria Emerge as Leaders in Leaderless Translation

The focal site of ribosome assembly and maturation in bacteria is the 5' untranslated region (UTR). Leaderless messenger RNAs (mRNAs) lack a 5' UTR and therefore present a conundrum for translation initiation. Leaderless mRNAs in Escherichia coli are rare and poorly translated, consistent with an inefficient by-product of the canonical mechanism. By contrast, transcription profiling approaches have unexpectedly found that leaderless mRNAs are both abundant and well-translated in certain bacterial clades, identifying those bacteria as leaderless adept. Mycobacteria are leaderless adept and offer multiple experimental model species that collectively broaden conclusions derived from leaderless translation studies. We review criteria derived from native mycobacterial mRNAs and from plasmid reporters expressed in mycobacteria that define leaderless mRNA features. We also look ahead at the unresolved conundrum of how leaderless mRNAs are efficiently translated. We anticipate that mycobacteria, along with diverse leaderless-adept Eubacteria and Archaea, will continue to make fundamental contributions in characterizing this major alternative mode of translation initiation.