The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript

Authors

  • Esmeralda Ramirez-Peña,

    1. Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
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  • Jeanette Treviño,

    1. Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
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  • Zhuyun Liu,

    1. Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
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  • Nataly Perez,

    1. Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
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  • Paul Sumby

    Corresponding authorSearch for more papers by this author

E-mail psumby@tmhs.org; Tel. (+1) 713 441 5897; Fax (+1) 713 441 7295.

Summary

Small RNA molecules play key regulatory roles in many bacterial species. However, little mechanistic data exists for the action of small regulatory RNAs in the human pathogen group A Streptococcus (GAS). Here, we analysed the relationship between a putative GAS sRNA and production of the secreted virulence factor streptokinase (SKA). SKA promotes GAS dissemination by activating conversion of host plasminogen into the fibrin-degrading protease plasmin. Homologues of the putative sRNA-encoding gene fibronectin/fibrinogen-binding/haemolytic-activity/streptokinase-regulator-X (fasX) were identified in four different pyogenic streptococcal species. However, despite 79% fasX nucleotide identity, a fasX allele from the animal pathogen Streptococcus zooepidemicus failed to complement a GAS fasX mutant. Using a series of precisely constructed fasX alleles we discovered that FasX is a bona-fide sRNA that post-transcriptionally regulates SKA production in GAS. By base-pairing to the 5′ end of ska mRNA, FasX enhances ska transcript stability, resulting in a ∼10-fold increase in SKA activity. Our data provide new insights into the mechanisms used by small regulatory RNAs to activate target mRNAs, and enhances our understanding of the regulation of a key GAS virulence factor.

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