title: The group A Streptococcus small regulatory RNA FasX enhances streptokinase activity by increasing the stability of the ska mRNA transcript.
abstract: 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.
authors.affiliation: Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Ramirez-Peña
authors.forename: Jeanette
authors.initials: J
authors.lastname: Treviño
authors.forename: Zhuyun
authors.initials: Z
authors.lastname: Liu
authors.forename: Nataly
authors.initials: N
authors.lastname: Perez
authors.forename: Paul
authors.initials: P
authors.lastname: Sumby
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020871:RNA Stability; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058727:RNA, Small Untranslated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013290:Streptococcal Infections / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D013300:Streptokinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; D058727:RNA, Small Untranslated; D037521:Virulence Factors; D013300:Streptokinase