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Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!

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  • Authors: Heather J. Beck1, Isabella Moll2
  • Editors: Gisela Storz3, Kai Papenfort4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Max F. Perutz Laboratories, Center for Molecular Biology, Department of Microbiology, Immunology and Genetics, University of Vienna, Vienna Biocenter, A-1030 Vienna, Austria; 2: Max F. Perutz Laboratories, Center for Molecular Biology, Department of Microbiology, Immunology and Genetics, University of Vienna, Vienna Biocenter, A-1030 Vienna, Austria; 3: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 4: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0016-2017
  • Received 28 November 2017 Accepted 20 February 2018 Published 06 July 2018
  • Isabella Moll, [email protected]
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  • Abstract:

    Previously, leaderless mRNAs (lmRNAs) were perceived to make up only a minor fraction of the transcriptome in bacteria. However, advancements in RNA sequencing technology are uncovering vast numbers of lmRNAs, particularly in archaea, , and extremophiles and thus underline their significance in cellular physiology and regulation. Due to the absence of conventional ribosome binding signals, lmRNA translation initiation is distinct from canonical mRNAs and can therefore be differentially regulated. The ribosome’s inherent ability to bind a 5′-terminal AUG can stabilize and protect the lmRNA from degradation or allow ribosomal loading for downstream initiation events. As a result, lmRNAs remain translationally competent during a variety of physiological conditions, allowing them to contribute to multiple regulatory mechanisms. Furthermore, the abundance of lmRNAs can increase during adverse conditions through the upregulation of lmRNA transcription from alternative promoters or by the generation of lmRNAs from canonical mRNAs cleaved by an endonucleolytic toxin. In these ways, lmRNA translation can continue during stress and contribute to regulation, illustrating their importance in the cell. Due to their presence in all domains of life and their ability to be translated by heterologous hosts, lmRNAs appear further to represent ancestral transcripts that might allow us to study the evolution of the ribosome and the translational process.

  • Citation: Beck H, Moll I. 2018. Leaderless mRNAs in the Spotlight: Ancient but Not Outdated!. Microbiol Spectrum 6(4):RWR-0016-2017. doi:10.1128/microbiolspec.RWR-0016-2017.

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/content/journal/microbiolspec/10.1128/microbiolspec.RWR-0016-2017
2018-07-06
2018-11-17

Abstract:

Previously, leaderless mRNAs (lmRNAs) were perceived to make up only a minor fraction of the transcriptome in bacteria. However, advancements in RNA sequencing technology are uncovering vast numbers of lmRNAs, particularly in archaea, , and extremophiles and thus underline their significance in cellular physiology and regulation. Due to the absence of conventional ribosome binding signals, lmRNA translation initiation is distinct from canonical mRNAs and can therefore be differentially regulated. The ribosome’s inherent ability to bind a 5′-terminal AUG can stabilize and protect the lmRNA from degradation or allow ribosomal loading for downstream initiation events. As a result, lmRNAs remain translationally competent during a variety of physiological conditions, allowing them to contribute to multiple regulatory mechanisms. Furthermore, the abundance of lmRNAs can increase during adverse conditions through the upregulation of lmRNA transcription from alternative promoters or by the generation of lmRNAs from canonical mRNAs cleaved by an endonucleolytic toxin. In these ways, lmRNA translation can continue during stress and contribute to regulation, illustrating their importance in the cell. Due to their presence in all domains of life and their ability to be translated by heterologous hosts, lmRNAs appear further to represent ancestral transcripts that might allow us to study the evolution of the ribosome and the translational process.

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Image of FIGURE 1
FIGURE 1

Mechanisms leading to the generation of lmRNAs in bacteria. Besides genes that are generally transcribed as lmRNAs, bacteria can generate lmRNAs in response to adverse environmental conditions (i) by activation of alternative promoters, where the transcriptional start point coincides with the A of the AUG start codon; (ii) by cotranscriptional cleavage, when the 5′ UTR is removed by RNases during the process of transcription; or (iii) cotranslationally. Here, the cleavage can be regulated by translating ribosomes that might either protect mRNAs from cleavage or expose specific sites for the processing event by RNases. Cleavage sites and potential RNases are indicated by red spheres and scissors, respectively.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0016-2017
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Image of FIGURE 2
FIGURE 2

Potential pathways for translation initiation complex (IC) formation on lmRNAs. (A) Schematic showing the main steps during canonical initiation. (B and C) Potential steps during translation initiation on lmRNAs via 30S subunits and 70S monosomes, respectively. r-Proteins bS1 and uS2 are transparent, indicating their dispensability during this process. See text for details.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0016-2017
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Tables

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TABLE 1

Compilation of published transcriptome analyses outlining the number of leaderless mRNAs in a variety of bacterial and archaeal genomes

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0016-2017

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