Regulation of morphological differentiation in S. coelicolor by RNase III (AbsB) cleavage of mRNA encoding the AdpA transcription factor.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Molecular Microbiology (Impact Factor: 5.03). 02/2010; 75(3):781-91. DOI: 10.1111/j.1365-2958.2009.07023.x
Source: PubMed

ABSTRACT RNase III family enzymes, which are perhaps the most widely conserved of all ribonucleases, are known primarily for their role in the processing and maturation of small RNAs. The RNase III gene of Streptomyces coelicolor, which was discovered initially as a global regulator of antibiotic production in this developmentally complex bacterial species and named absB (antibiotic biosynthesis gene B), has subsequently also been found to modulate the cellular abundance of multiple messenger RNAs implicated in morphological differentiation. We report here that regulation of differentiation-related mRNAs by the S. coelicolor AbsB/RNase III enzyme occurs largely by ribonucleolytic cleavage of transcripts encoding the pleiotropic transcription factor, AdpA, and that AdpA and AbsB participate in a novel feedback-control loop that reciprocally regulates the cellular levels of both proteins. Our results reveal a previously unsuspected mechanism for global ribonuclease-mediated control of gene expression in streptomycetes.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To illuminate the evolution and mechanisms of actinobacterial complexity, we evaluate the distribution and origins of known Streptomyces developmental genes, and the developmental significance of actinobacteria-specific genes. As an aid, we developed the Actinoblast database of reciprocal BlastP best-hits between the Streptomyces coelicolor genome and more than 100 other actinobacterial genomes ( We suggest that the emergence of morphological complexity was underpinned by special features of early actinobacteria, such as polar growth and the coupled participation of regulatory Wbl proteins and the redox-protecting thiol mycothiol in transducing a transient nitric oxide signal generated during physiologically stressful growth transitions. It seems that some cell growth and division proteins of early actinobacteria have acquired greater importance for sporulation of complex actinobacteria than for mycelial growth, in which septa are infrequent and not associated with complete cell separation. The acquisition of extracellular proteins with structural roles, a highly regulated extracellular protease cascade, and additional regulatory genes allowed early actinobacterial stationary-phase processes to be redeployed in the emergence of aerial hyphae from mycelial mats and in the formation of spore chains. These extracellular proteins may have contributed to speciation. Simpler members of morphologically diverse clades have lost some developmental genes. This article is protected by copyright. All rights reserved.
    FEMS microbiology reviews 10/2013; · 10.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The angucycline antibiotic jadomycin B (JdB) produced by Streptomyces venezuelae has been found here to induce complex survival responses in Streptomyces coelicolor at subinhibitory concentration. The receptor for JdB was identified as a "pseudo" gamma-butyrolactone receptor, ScbR2, which was shown to bind two previously unidentified target promoters, those of redD (redDp) and adpA (adpAp), thus directly regulating undecylprodigiosin (Red) production and morphological differentiation, respectively. Because AdpA also directly regulates the expression of redD, ScbR2, AdpA, and RedD together form a feed-forward loop controlling both differentiation and Red production phenotypes. Different signal strengths (i.e., JdB concentrations) were shown to induce the two different phenotypes by modulating the relative transcription levels of adpA vs. redD. The induction of morphological differentiation and endogenous antibiotic production by exogenous antibiotic exemplifies an important survival strategy more sophisticated than the induction of antibiotic resistance.
    Proceedings of the National Academy of Sciences 03/2014; · 9.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AdpA is a global transcriptional regulator that is induced by the microbial hormone A-factor and activates many genes required for morphological differentiation and secondary metabolism in Streptomyces griseus. We confirmed that the regulatory tRNA gene bldA was required for translation of TTA-containing adpA. We also demonstrated that AdpA bound two sites upstream of the bldA promoter and activated transcription of bldA. Thus, we revealed a unique positive feedback loop between AdpA and BldA in S. griseus. Forced expression of bldA in an A-factor-deficient mutant resulted in the partial restoration of aerial mycelium formation and streptomycin production, suggesting that the positive feedback loop could prevent premature transcriptional activation of the AdpA-target genes in the wild-type strain. We revealed that the morphological defect of the bldA mutant could be attributed mainly to the TTA codons of only two genes: adpA and amfR. amfR encodes a transcriptional activator essential for aerial mycelium formation and is a member of the AdpA regulon. Thus, amfR is regulated by a feedforward mechanism involving AdpA and BldA. We concluded that the central regulatory unit composed of AdpA and BldA plays important roles in the initiation of morphological differentiation and secondary metabolism triggered by A-factor.
    Molecular Microbiology 09/2011; 81(6):1607-22. · 5.03 Impact Factor


Available from