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: 4.42). 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.

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Available from: Jing Shi, Jan 14, 2015
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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.
    Advances in applied microbiology 08/2014; 89:217-66. DOI:10.1016/B978-0-12-800259-9.00006-8 · 2.74 Impact Factor
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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.
    BMC Microbiology 04/2014; 14(1):81. DOI:10.1186/1471-2180-14-81 · 2.73 Impact Factor
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    • "Collectively, these trends demonstrate the contribution of targeted mRNA degradation to the transcriptional bottleneck and the modulation of genetic programs subsequently deployed (Figure 4). They also anticipate a pivotal and global role for ribonucleases, such as RNase E and III, in regulating the metabolic switch [21,22,27,28]. "
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    ABSTRACT: Background Actinobacteria form a major bacterial phylum that includes numerous human pathogens. Actinobacteria are primary contributors to carbon cycling and also represent a primary source of industrial high value products such as antibiotics and biopesticides. Consistent with other members of the actinobacterial phylum, Saccharopolyspora erythraea undergo a transitional switch. This switch is characterized by numerous metabolic and morphological changes. Results We performed RNA sequencing to analyze the transcriptional changes that occur during growth of Saccharopolyspora erythraea in batch culture. By sequencing RNA across the fermentation time course, at a mean coverage of 4000X, we found the vast majority of genes to be prominently expressed, showing that we attained close to saturating sequencing coverage of the transcriptome. During the metabolic switch, global changes in gene expression influence the metabolic machinery of Saccharopolyspora erythraea, resetting an entirely novel gene expression program. After the switch, global changes include the broad repression of half the genes regulated by complex transcriptional mechanisms. Paralogous transposon clusters, delineate these transcriptional programs. The new transcriptional program is orchestrated by a bottleneck event during which mRNA levels are severely restricted by targeted mRNA degradation. Conclusions Our results, which attained close to saturating sequencing coverage of the transcriptome, revealed unanticipated transcriptional complexity with almost one third of transcriptional content originating from un-annotated sequences. We showed that the metabolic switch is a sophisticated mechanism of transcriptional regulation capable of resetting and re-synchronizing gene expression programs at extraordinary speed and scale.
    BMC Genomics 01/2013; 14(1):15. DOI:10.1186/1471-2164-14-15 · 3.99 Impact Factor
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