Xu, W., Huang, J., Lin, R., Shi, J. & Cohen, S. N Regulation of morphological differentiation in S. coelicolor by RNase III (AbsB) cleavage of mRNA encoding the AdpA transcription factor. Mol. Microbiol. 75, 781-791

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Molecular Microbiology (Impact Factor: 4.42). 02/2010; 75(3):781-91. DOI: 10.1111/j.1365-2958.2009.07023.x
Source: PubMed


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.

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Available from: Jing Shi, Jan 14, 2015
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    • "morphological development is mediated by RNase III cleavage of mRNA encoding the AdpA transcription factor (Xu et al., 2010). AdpA plays a key role in the regulation of both morphological differentiation and secondary metabolite biosynthesis (Xu et al., 2010). Some RNase mutants show defects in cell morphology of Escherichia coli and Bacillus subtilis. "
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    ABSTRACT: The Corynebacterium glutamicum R cgR_1959 gene encodes an endoribonuclease of the RNase III family. Deletion mutant of cgR_1959 (Δrnc mutant) showed an elongated cell shape, and presence of several lines on the cell surface, indicating a required of RNase III for maintaining normal cell morphology in C. glutamicum. The level of mraZ mRNA was increased, whereas cgR_1596 mRNA encoding a putative cell wall hydrolase and ftsEX mRNA were decreased in the Δrnc mutant. The half-life of mraZ mRNA was significantly prolonged in the Δrnc and the Δpnp mutant strains. This indicated that the degradation of mraZ mRNA was performed by RNase III and the 3'-to-5' exoribonuclease, PNPase. Northern hybridization and primer extension analysis revealed that the cleavage site for mraZ mRNA by RNase III is in the coding region. Overproduction of MraZ resulted in an elongated cell shape. The expression of ftsEX decreased while that of cgR_1596 unchanged in an MraZ-overexpressing strain. An electrophoretic mobility shift assay and a transcriptional reporter assay indicate that MraZ is a transcriptional repressor of ftsEX in C. glutamicum. These results indicate that RNase III is required for efficient expression of MraZ-dependent ftsEX and MraZ-independent cgR_1596. This article is protected by copyright. All rights reserved.
    Full-text · Article · Dec 2015 · Molecular Microbiology
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    • "Relief of ScbR2 binding to the cpkO promoter has also been observed by adding Act ( and Red , although the data for this ambiguous ) , and it is pos - tulated that this antibiotic may be a ScbR2 ligand , indicating another pos - sible mechanism of regulatory cross talk between different antibiotic biosynthetic pathways ( Xu , Huang , et al . , 2010 ) . The γ - butyrolactones represent important small autoregulatory molecules controlling antibiotic biosynthesis . Production of Mmy , encoded by the mmy gene cluster on the plasmid SCP1 , is controlled in a similar manner by similar , but different , chemical entities , the MMF furans ( Corre et al . , 2008 ) , see also Section 4 . 1 "
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    ABSTRACT: The actinomycetes are well-known bioactive natural product producers, comprising the Streptomycetes, the richest drug-prolific family in all kingdoms, producing therapeutic compounds for the areas of infection, cancer, circulation, and immunity. Completion and annotation of many actinomycete genomes has highlighted further how proficient these bacteria are in specialized metabolism, which have been largely underexploited in traditional screening programs. The genome sequence of the model strain Streptomyces coelicolor A3(2), and subsequent development of genomics-driven approaches to understand its large specialized metabolome, has been key in unlocking the high potential of specialized metabolites for natural product genomics-based drug discovery. This review discusses systematically the biochemistry and genetics of each of the specialized metabolites of S. coelicolor and describes metabolite transport processes for excretion and complex regulatory patterns controlling biosynthesis.
    Full-text · Article · Aug 2014 · Advances in applied microbiology
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    • "In S. coelicolor, BldD represses adpA expression [21]. At the translational level, a feedback-control loop regulates levels of AdpA and AbsB (a RNAse III) in S. coelicolor[22,23]. A positive feedback loop between AdpA and BldA, the only tRNA able to read the UUA codon present in all adpA mRNA, has been demonstrated in S. griseus[22,23]. "
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    ABSTRACT: AdpA is a key transcriptional regulator involved in the complex growth cycle of Streptomyces. Streptomyces are Gram-positive bacteria well-known for their production of secondary metabolites and antibiotics. Most work on AdpA has been in S. griseus, and little is known about the pathways it controls in other Streptomyces spp. We recently discovered interplay between ClpP peptidases and AdpA in S. lividans. Here, we report the identification of genes directly regulated by AdpA in S. lividans. Microarray experiments revealed that the expression of hundreds of genes was affected in a S. lividans adpA mutant during early stationary phase cultures in YEME liquid medium. We studied the expression of the S. lividans AdpA-regulated genes by quantitative real-time PCR analysis after various times of growth. In silico analysis revealed the presence of potential AdpA-binding sites upstream from these genes; electrophoretic mobility shift assays indicated that AdpA binds directly to their promoter regions. This work identifies new pathways directly controlled by AdpA and that are involved in S. lividans development (ramR, SLI7885 also known as hyaS and SLI6586), and primary (SLI0755-SLI0754 encoding CYP105D5 and Fdx4) or secondary (cchA, cchB, and hyaS) metabolism. We characterised six S. lividans AdpA-dependent genes whose expression is directly activated by this pleiotropic regulator. Several of these genes are orthologous to bldA-dependent genes in S. coelicolor. Furthermore, in silico analysis suggests that over hundred genes may be directly activated or repressed by S. lividans AdpA, although few have been described as being part of any Streptomyces AdpA regulons. This study increases the number of known AdpA-regulated pathways in Streptomyces spp.
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