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Added value of autoregulation and multi-step kinetics of transcription initiation

2018-11-01Artigo científico Acesso aberto
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dc.contributor.authorPrajapat, Mahendra Kumar
dc.contributor.authorRibeiro, André S.
dc.contributor.institutionCTS - Centro de Tecnologia e Sistemas
dc.contributor.institutionUNINOVA-Instituto de Desenvolvimento de Novas Tecnologias
dc.contributor.pblRoyal Society
dc.date.accessioned2019-06-17T22:44:44Z
dc.date.available2019-06-17T22:44:44Z
dc.date.issued2018-11-01
dc.descriptionThis work was supported by Tekniikan edistamissaation (M.K.P), Academy of Finland (295027 to A.S.R.), Academy of Finland Key Project Funding (305342 to A.S.R.) and Jane and Aatos Erkko Foundation (610536 to A.S.R.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
dc.description.abstractBacterial gene expression regulation occurs mostly during transcription, which has two main rate-limiting steps: the close complex formation, when the RNA polymerase binds to an active promoter, and the subsequent open complex formation, after which it follows elongation. Tuning these steps’ kinetics by the action of e.g. transcription factors, allows for a wide diversity of dynamics. For example, adding autoregulation generates single-gene circuits able to perform more complex tasks. Using stochastic models of transcription kinetics with empirically validated parameter values, we investigate how autoregulation and the multi-step transcription initiation kinetics of single-gene autoregulated circuits can be combined to fine-tune steady state mean and cell-to-cell variability in protein expression levels, as well as response times. Next, we investigate how they can be jointly tuned to control complex behaviours, namely, time counting, switching dynamics and memory storage. Overall, our finding suggests that, in bacteria, jointly regulating a single-gene circuit’s topology and the transcription initiation multi-step dynamics allows enhancing complex task performance.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2412677
dc.identifier.doi10.1098/rsos.181170
dc.identifier.issn2054-5703
dc.identifier.otherPURE: 13707083
dc.identifier.otherPURE UUID: 49a6c035-b4cf-450e-bc5f-d269c61be0cc
dc.identifier.otherScopus: 85058415001
dc.identifier.otherPubMed: 30564410
dc.identifier.otherPubMedCentral: PMC6281912
dc.identifier.otherWOS: 000451777500031
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=85058415001&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/85058415001
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAutoregulation mechanisms
dc.subjectCell-to-cell variability
dc.subjectRate-limiting steps
dc.subjectTranscription initiation
dc.subjectGeneral
dc.titleAdded value of autoregulation and multi-step kinetics of transcription initiationen
dc.typejournal article
degois.publication.issue11
degois.publication.titleRoyal Society Open Science
degois.publication.volume5
dspace.entity.typePublication
rcaap.rightsopenAccess

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