Riboswitch-Mediated Gene Regulation: Novel RNA Architectures Dictate Gene Expression Responses

Sherwood, Anna V.; Henkin, Tina M.

doi:10.1146/annurev-micro-091014-104306

Cited by 201 publications

(174 citation statements)

References 74 publications

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“…Though these 5' UTRs are not conserved on the sequence level, their occurrence in every PLE suggests conservation of function. The 5' UTR of transcripts is a common site for riboswitches [52] suggesting that these untranslated sequences may regulate expression of their downstream genes.…”

Section: Non-coding Rnas Are Abundant In Icp1 and Plesmentioning

confidence: 99%

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Barth

Netter

Angermeyer

et al. 2020

Preprint

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Many viruses possess temporally unfolding gene expression patterns aimed at subverting host defenses, commandeering host metabolism, and ultimately producing a large number of progeny virions. High throughput -omics tools, such as RNA-seq, have dramatically enhanced resolution of expression patterns during infection. Less studied have been viral satellites, mobile genomes that parasitize viruses and have far reaching effects on host-cell fitness. By performing RNA-seq on infection time courses, we have obtained the first time-resolved transcriptomes for bacteriophage satellites during lytic infection. Specifically, we have acquired transcriptomes for the lytic Vibrio cholerae phage ICP1 and all five known variants of ICP1's parasite, the Phage Inducible Chromosomal Island-Like Elements (PLEs). PLEs rely on ICP1 for both DNA replication and mobilization, and abolish production of ICP1 progeny in infected cells. We investigated PLEs impact on ICP1 gene expression and found that PLEs did not broadly restrict or reduce ICP1 gene expression. A major exception occurred in ICP1's capsid morphogenesis operon, which was downregulated by each of the PLE variants. This transcriptional manipulation, conserved among PLEs, has also evolved independently in at least one other phage satellite, suggesting that viral satellites may be under strong selective pressure to reduce the capsid expression of their larger host viruses. Surprisingly, PLEs were also found to alter the gene expression of CTXφ, the integrative phage that encodes cholera toxin and is necessary for virulence of toxigenic V. cholerae. One PLE, PLE1, upregulated CTXφ genes involved in replication and integration, and boosted CTXφ mobility following induction of the SOS response. Our data show that PLEs exhibit conserved manipulation of their host-phage's gene expression, but divergent effects on CTXφ, revealing that PLEs can influence both their hosts' resistance to phage and the mobility of virulence encoding elements.So far, few insights have been gained into the gene expression programs of ICP1 and PLEs. PLE1 expresses its integrase in uninfected cells [22], expression of PLE1's replication initiator, RepA, is induced following infection of ICP1 [23], and the PLE's lysis modulator, LidI, is detectable by Western blot late during ICP1 infection [25]. The PLE integrase's recombination directionality factor (necessary for directing integrase excision activity) is PexA, an ICP1 protein whose native function is unknown, but whose expression can be detected by 5 minutes post infection [22]. While these limited observations have provided insight into key PLE and ICP1 genes, the gross expression patterns of ICP1 and PLEs remain unknown. Until now, we have not known the degree to which ICP1 alters cellular expression patterns, and whether PLEs alter ICP1's gene expression or reproduce and restrict ICP1 without such alterations. To address these questions, we performed RNA-seq on V. cholerae infected by ICP1 over the course of the infection cycle. We sequenced the transc...

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Section: Non-coding Rnas Are Abundant In Icp1 and Plesmentioning

confidence: 99%

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Barth

Netter

Angermeyer

et al. 2020

Preprint

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“…Upon sensing changes in levels of a particular metabolite, it regulates the level of transcription or translation of a downstream mRNA sequence (1–3). Riboswitches are widespread in gram positive bacteria and are considered good targets for inhibitor design as they regulate genes or operons involved in utilization, biosynthesis or transport of essential cellular metabolites (4).…”

Section: Introductionmentioning

confidence: 99%

Molecular envelope and atomic model of an anti-terminated glyQS T-box regulator in complex with tRNAGly

Chetnani

Mondragón

2017

Nucleic Acids Research

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A T-box regulator or riboswitch actively monitors the levels of charged/uncharged tRNA and participates in amino acid homeostasis by regulating genes involved in their utilization or biosynthesis. It has an aptamer domain for cognate tRNA recognition and an expression platform to sense the charge state and modulate gene expression. These two conserved domains are connected by a variable linker that harbors additional secondary structural elements, such as Stem III. The structural basis for specific tRNA binding is known, but the structural basis for charge sensing and the role of other elements remains elusive. To gain new structural insights on the T-box mechanism, a molecular envelope was calculated from small angle X-ray scattering data for the Bacillus subtilis glyQS T-box riboswitch in complex with an uncharged tRNAGly. A structural model of an anti-terminated glyQS T-box in complex with its cognate tRNAGly was derived based on the molecular envelope. It shows the location and relative orientation of various secondary structural elements. The model was validated by comparing the envelopes of the wild-type complex and two variants. The structural model suggests that in addition to a possible regulatory role, Stem III could aid in preferential stabilization of the T-box anti-terminated state allowing read-through of regulated genes.

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“…1A) (Belitsky et al, 2001). A common denominator of proBA and proI transcription is their control via a T-box system (Brill et al, 2011b), an RNA-based regulatory device (Sherwood and Henkin, 2016) that gauges cellular proline pools through the loading-status of a proline-specific tRNA and its interaction with a particular proline-specific codon in the 5' non-translated regions of the proBA and proI genes (Brill et al, 2011b). The proline-responsive T-box system allows enhanced full-length proBA and proI transcription only when the proline pool of the cell is insufficient for adequate protein biosynthesis (Brill et al, 2011b).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the compatible solute proline by Bacillus subtilis: point mutations rendering the osmotically controlled proHJ promoter hyperactive

Hoffmann

Bleisteiner

Sappa

et al. 2017

Environmental Microbiology

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The ProJ and ProH enzymes of Bacillus subtilis catalyse together with ProA (ProJ-ProA-ProH), osmostress-adaptive synthesis of the compatible solute proline. The proA-encoded gamma-glutamyl phosphate reductase is also used for anabolic proline synthesis (ProB-ProA-ProI). Transcription of the proHJ operon is osmotically inducible whereas that of the proBA operon is not. Targeted and quantitative proteome analysis revealed that the amount of ProA is not limiting for the interconnected anabolic and osmostress-responsive proline production routes. A key player for enhanced osmostress-adaptive proline production is the osmotically regulated proHJ promoter. We used site-directed mutagenesis to study the salient features of this stress-responsive promoter. Two important features were identified: (i) deviations of the proHJ promoter from the consensus sequence of SigA-type promoters serve to keep transcription low under non-inducing growth conditions, while still allowing a finely tuned induction of transcriptional activity when the external osmolarity is increased and (ii) a suboptimal spacer length for SigA-type promoters of either 16-bp (the natural proHJ promoter), or 18-bp (a synthetic promoter variant) is strictly required to allow regulation of promoter activity in proportion to the external salinity. Collectively, our data suggest that changes in the local DNA structure at the proHJ promoter are important determinants for osmostress-inducibility of transcription.

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Riboswitch-Mediated Gene Regulation: Novel RNA Architectures Dictate Gene Expression Responses

Cited by 201 publications

References 74 publications

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

Molecular envelope and atomic model of an anti-terminated glyQS T-box regulator in complex with tRNAGly

Synthesis of the compatible solute proline by Bacillus subtilis: point mutations rendering the osmotically controlled proHJ promoter hyperactive

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