{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:42:07Z","timestamp":1767181327348,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011738","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21721003, 12234019 and 32000888"],"award-info":[{"award-number":["21721003, 12234019 and 32000888"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jilin Province Science and Technology Development Plan","award":["20200301009RQ"],"award-info":[{"award-number":["20200301009RQ"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Elevated CO\n                    <jats:sub>2<\/jats:sub>\n                    concentrations have been observed to accelerate flowering time in Arabidopsis through the action of a highly conserved regulatory network controlled by miR156 and miR172. However, the network\u2019s robustness to the impact of increasing CO\n                    <jats:sub>2<\/jats:sub>\n                    concentrations on flowering time remains poorly understood. In this study, we investigate this question by conducting a comprehensive analysis of the global landscape of network dynamics, including quantifying the probabilities associated with juvenile and flowering states and assessing the speed of the transition between them. Our findings reveal that a CO\n                    <jats:sub>2<\/jats:sub>\n                    concentration range of 400\u2013800ppm only mildly advances flowering time, contrasting with the dramatic changes from 200 to 300ppm. Notably, the feedback regulation of miR156 by squamosal promoter binding protein-like proteins (SPLs) plays a substantial role in mitigating the effects of increasing CO\n                    <jats:sub>2<\/jats:sub>\n                    on flowering time. Intriguingly, we consistently observe a correlation between delayed flowering time and increased variance in flowering time, and vice versa, suggesting that this might be an intrinsic adaptation mechanism embedded within the network. To gain a deeper understanding of this network\u2019s dynamics, we identified the sensitive features within the feedback loops of miR156 SPLs and miR172\u2014APETALA2 family proteins (AP2s), with the latter proving to be the most sensitive. Strikingly, our study underscores the indispensability of all feedback regulations in maintaining both juvenile and adult states as well as the transition time between them. Together, our research provides the first physical basis in plant species, aiding in the elucidation of novel regulatory mechanisms and the robustness of the miRNAs-regulated network in response to increasing CO\n                    <jats:sub>2<\/jats:sub>\n                    , therefore influencing the control of flowering time. Moreover, this study provides a promising strategy for engineering plant flowering time to enhance their adaptation and resilience.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1011738","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T13:43:27Z","timestamp":1703079807000},"page":"e1011738","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["High CO2 adaptation mechanisms revealed in the miR156-regulated flowering time pathway"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-4511","authenticated-orcid":true,"given":"Kun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erkang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4636-0920","authenticated-orcid":true,"given":"Qiong Alison","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-4913","authenticated-orcid":true,"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"issue":"3","key":"pcbi.1011738.ref001","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1469-8137.2006.01806.x","article-title":"The small RNA world of plants","volume":"171","author":"E Bonnet","year":"2006","journal-title":"New Phytol"},{"issue":"2","key":"pcbi.1011738.ref002","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target Recognition and Regulatory Functions","volume":"136","author":"DP Bartel","year":"2009","journal-title":"Cell"},{"key":"pcbi.1011738.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gde.2014.03.005","article-title":"MicroRNAs and their roles in developmental canalization","volume":"27","author":"DM Posadas","year":"2014","journal-title":"Curr Opin Genet Dev"},{"key":"pcbi.1011738.ref004","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-arplant-050718-100334","article-title":"MicroRNAs and Their Regulatory Roles in Plant-Environment Interactions.","volume":"7070","author":"XW Song","year":"2019","journal-title":"Annual Review of Plant Biology"},{"issue":"12","key":"pcbi.1011738.ref005","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1007\/s00018-011-0673-y","article-title":"Regulation of flowering time: all roads lead to Rome","volume":"68","author":"A Srikanth","year":"2011","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"pcbi.1011738.ref006","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2009.06.031","article-title":"The Sequential Action of miR156 and miR172 Regulates Developmental Timing in Arabidopsis","volume":"138","author":"G Wu","year":"2009","journal-title":"Cell"},{"issue":"2","key":"pcbi.1011738.ref007","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/jxb\/erq295","article-title":"Regulation of flowering time and floral patterning by miR172","volume":"62","author":"Q-H Zhu","year":"2011","journal-title":"J Exp Bot"},{"key":"pcbi.1011738.ref008","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/B978-0-12-396968-2.00005-1","article-title":"Vegetative Phase Change and Shoot Maturation in Plants","volume":"105","author":"RS Poethig","year":"2013","journal-title":"Curr Top Dev Biol"},{"issue":"4","key":"pcbi.1011738.ref009","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1365-313X.2006.02983.x","article-title":"The miRNA156\/157 recognition element in the 3\u2019 UTR of the Arabidopsis SBP box gene prevents early flowering by translational inhibition in seedlings","volume":"49","author":"M Gandikota","year":"2007","journal-title":"Plant J"},{"issue":"4","key":"pcbi.1011738.ref010","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.cell.2009.06.014","article-title":"miR156-Regulated SPL Transcription Factors Define an Endogenous Flowering Pathway in Arabidopsis thaliana","volume":"138","author":"JW Wang","year":"2009","journal-title":"Cell"},{"issue":"12","key":"pcbi.1011738.ref011","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1093\/pcp\/pcp148","article-title":"Arabidopsis SBP-Box Genes and Control Morphological Change in Association with Shoot Maturation in the Reproductive Phase","volume":"50","author":"M Shikata","year":"2009","journal-title":"Plant and Cell Physiology"},{"issue":"19","key":"pcbi.1011738.ref012","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1242\/dev.063511","article-title":"The control of developmental phase transitions in plants","volume":"138","author":"P Huijser","year":"2011","journal-title":"Development"},{"issue":"2","key":"pcbi.1011738.ref013","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1017\/S0960258510000073","article-title":"The regulation of post-germinative transition from the cotyledon- to vegetative-leaf stages by microRNA-targeted SQUAMOSA PROMOTER-BINDING PROTEIN LIKE13 in Arabidopsis in Arabidopsis.","volume":"20","author":"RC Martin","year":"2010","journal-title":"Seed Sci Res"},{"issue":"1\u20132","key":"pcbi.1011738.ref014","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11103-008-9310-z","article-title":"The microRNA regulated SBP-box genes SPL9 and SPL15 control shoot maturation in Arabidopsis","volume":"67","author":"S Schwarz","year":"2008","journal-title":"Plant Mol Biol"},{"issue":"1\u20132","key":"pcbi.1011738.ref015","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11103-011-9759-z","article-title":"miR172 signals are incorporated into the miR156 signaling pathway at the SPL3\/4\/5 genes in Arabidopsis developmental transitions","volume":"76","author":"JH Jung","year":"2011","journal-title":"Plant Mol Biol"},{"issue":"7","key":"pcbi.1011738.ref016","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1105\/tpc.110.075606","article-title":"Orchestration of the Floral Transition and Floral Development in Arabidopsis by the Bifunctional Transcription Factor APETALA2","volume":"22","author":"L Yant","year":"2010","journal-title":"The Plant Cell"},{"issue":"7","key":"pcbi.1011738.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000148","article-title":"Repression of Flowering by the miR172 Target SMZ.","volume":"7","author":"J Mathieu","year":"2009","journal-title":"PLoS Biol"},{"issue":"4","key":"pcbi.1011738.ref018","first-page":"e9580010","article-title":"A Comprehensive Genome-Wide Study on Tissue-Specific and Abiotic Stress-Specific miRNAs in Triticum aestivum.","volume":"9","author":"R Pandey","year":"2014"},{"issue":"6","key":"pcbi.1011738.ref019","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/tpj.12712","article-title":"The pathway coordinates the relationship between development and abiotic stress tolerance in plants","volume":"80","author":"LG Cui","year":"2014","journal-title":"Plant J"},{"key":"pcbi.1011738.ref020","article-title":"The effects of carbon dioxide and temperature on microRNA expression in Arabidopsis development","volume":"4","author":"P May","year":"2013","journal-title":"Nat Commun"},{"key":"pcbi.1011738.ref021","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.00260","article-title":"Sugar promotes vegetative phase change in Arabidopsis thaliana by repressing the expression of MIR156A and MIR156C.","volume":"2","author":"L Yang","year":"2013","journal-title":"Elife"},{"issue":"3","key":"pcbi.1011738.ref022","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s13562-012-0163-9","article-title":"Hexokinase from grape berries: its prokaryotic expression, polyclonal antibody preparation and biochemical property analyses.","volume":"22","author":"F Yu","year":"2013","journal-title":"J Plant Biochem Biot"},{"issue":"6120","key":"pcbi.1011738.ref023","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1126\/science.1230406","article-title":"Regulation of Flowering by Trehalose-6-Phosphate Signaling in.","volume":"339","author":"V Wahl","year":"2013","journal-title":"Science"},{"issue":"4","key":"pcbi.1011738.ref024","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.gde.2009.06.001","article-title":"Small RNAs and developmental timing in plants","volume":"19","author":"RS Poethig","year":"2009","journal-title":"Curr Opin Genet Dev"},{"key":"pcbi.1011738.ref025","article-title":"The Strategy of the Genes.","author":"CH Waddington","year":"1957","journal-title":"(Allen &Unwin, London)"},{"issue":"1","key":"pcbi.1011738.ref026","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00018732.2015.1037068","article-title":"Landscape and flux theory of non-equilibrium dynamical systems with application to biology","volume":"64","author":"J. Wang","year":"2015","journal-title":"Adv Phys"},{"issue":"34","key":"pcbi.1011738.ref027","doi-asserted-by":"crossref","first-page":"12271","DOI":"10.1073\/pnas.0800579105","article-title":"Potential landscape and flux framework of nonequilibrium networks: robustness, dissipation, and coherence of biochemical oscillations","volume":"105","author":"J Wang","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"20","key":"pcbi.1011738.ref028","doi-asserted-by":"crossref","first-page":"8257","DOI":"10.1073\/pnas.1017017108","article-title":"Quantifying the Waddington landscape and biological paths for development and differentiation","volume":"108","author":"J Wang","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"issue":"42","key":"pcbi.1011738.ref029","doi-asserted-by":"crossref","first-page":"13164","DOI":"10.1021\/jp403156m","article-title":"Tristability in Cancer-Associated MicroRNA-TF Chimera Toggle Switch","volume":"117","author":"MY Lu","year":"2013","journal-title":"J Phys Chem B"},{"issue":"4","key":"pcbi.1011738.ref030","first-page":"85","article-title":"Mechanisms generating bistability and oscillations in microRNA-mediated motifs","author":"PP Zhou","year":"2012","journal-title":"Phys Rev E"},{"issue":"9","key":"pcbi.1011738.ref031","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/ng.905","article-title":"MicroRNAs can generate thresholds in target gene expression","volume":"43","author":"S Mukherji","year":"2011","journal-title":"Nat Genet"},{"key":"pcbi.1011738.ref032","volume-title":"Stochastic Processes in Chemistry and Physics. North-Holland","author":"N. Van Kampen","year":"1992"},{"issue":"2","key":"pcbi.1011738.ref033","article-title":"MiRNA Control of Vegetative Phase Change in Trees","volume":"7","author":"JW Wang","year":"2011","journal-title":"PLoS Genet"},{"issue":"6","key":"pcbi.1011738.ref034","article-title":"The Control of Developmental Phase Transitions by microRNAs and Their Targets in Seed Plants.","volume":"21","author":"JY Ma","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pcbi.1011738.ref035","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/wrna.1215","article-title":"Genetic regulation of flowering time in annual and perennial plants","volume":"5","author":"MRG Khan","year":"2014","journal-title":"Wires Rna"},{"issue":"3","key":"pcbi.1011738.ref036","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.molp.2014.12.018","article-title":"To Bloom or Not to Bloom: Role of MicroRNAs in Plant Flowering.","volume":"8","author":"S Teotia","year":"2015","journal-title":"Molecular Plant."},{"issue":"2","key":"pcbi.1011738.ref037","first-page":"137","article-title":"Role of miRNAs and siRNAs in biotic and abiotic stress responses of plants.","volume":"1819","author":"B Khraiwesh","year":"2012","journal-title":"Bba-Gene Regul Mech"},{"issue":"4","key":"pcbi.1011738.ref038","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.202002","article-title":"miRNA targeting and alternative splicing in the stress response\u2014events hosted by membrane-less compartments","volume":"131","author":"MM Kucherenko","year":"2018","journal-title":"J Cell Sci"},{"issue":"7","key":"pcbi.1011738.ref039","article-title":"microRNAs as Developmental Regulators.","volume":"7","author":"KN Ivey","year":"2015","journal-title":"Csh Perspect Biol."},{"issue":"2","key":"pcbi.1011738.ref040","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/jcp.25125","article-title":"MicroRNAs in Control of Plant Development","volume":"231","author":"C Li","year":"2016","journal-title":"Journal of Cellular Physiology"},{"issue":"44","key":"pcbi.1011738.ref041","doi-asserted-by":"crossref","first-page":"18668","DOI":"10.1073\/pnas.0908131106","article-title":"A feedback circuit involving let-7-family miRNAs and DAF-12 integrates environmental signals and developmental timing in Caenorhabditis elegans","volume":"106","author":"CM Hammell","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"pcbi.1011738.ref042","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.gde.2011.04.003","article-title":"MicroRNAs and developmental timing","volume":"21","author":"V. Ambros","year":"2011","journal-title":"Curr Opin Genet Dev"},{"issue":"13","key":"pcbi.1011738.ref043","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1101\/gad.1937010","article-title":"MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems","volume":"24","author":"H Herranz","year":"2010","journal-title":"Genes Dev"},{"key":"pcbi.1011738.ref044","first-page":"498","article-title":"Nonlinear dynamics and Chaos: with applications to physics, biology, chemistry, and engineering.","volume":"xi","author":"SH Strogatz","year":"1994","journal-title":"Reading, Mass.: Addison-Wesley Pub"},{"issue":"12","key":"pcbi.1011738.ref045","article-title":"Noise Propagation in Gene Regulation Networks Involving Interlinked Positive and Negative Feedback Loops.","volume":"7","author":"H Zhang","year":"2012","journal-title":"Plos One"},{"key":"pcbi.1011738.ref046","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fgene.2013.00305","article-title":"Stress-induced ECM alteration modulates cellular microRNAs that feedback to readjust the extracellular environment and cell behavior","volume":"4","author":"EV Edeleva","year":"2013","journal-title":"Frontiers in Genetics"},{"issue":"9","key":"pcbi.1011738.ref047","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1105\/tpc.107.054528","article-title":"The GIGANTEA-regulated MicroRNA172 mediates photoperiodic flowering independent of CONSTANS in Arabidopsis","volume":"19","author":"JH Jung","year":"2007","journal-title":"Plant Cell"},{"issue":"11","key":"pcbi.1011738.ref048","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1105\/tpc.016238","article-title":"Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-like target genes","volume":"15","author":"MJ Aukerman","year":"2003","journal-title":"Plant Cell"},{"issue":"5666","key":"pcbi.1011738.ref049","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1126\/science.1088060","article-title":"A microRNA as a translational repressor of APETALA2 in Arabidopsis flower development","volume":"303","author":"XM Chen","year":"2004","journal-title":"Science"},{"issue":"6806","key":"pcbi.1011738.ref050","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/35038000","article-title":"Glacial\/interglacial variations in atmospheric carbon dioxide","volume":"407","author":"DM Sigman","year":"2000","journal-title":"Nature"},{"issue":"2","key":"pcbi.1011738.ref051","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1469-8137.2007.02196.x","article-title":"Flowering time and elevated atmospheric CO2","volume":"176","author":"CJ Springer","year":"2007","journal-title":"New Phytol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011738","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T13:30:45Z","timestamp":1704807045000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011738"}},"subtitle":[],"editor":[{"given":"Venugopala Reddy","family":"Gonehal","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011738","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]}}}