{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:13:26Z","timestamp":1772172806056,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008828","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-1840273"],"award-info":[{"award-number":["MCB-1840273"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Multinucleate cells occur in every biosphere and across the kingdoms of life, including in the human body as muscle cells and bone-forming cells. Data from filamentous fungi suggest that, even when bathed in a common cytoplasm, nuclei are capable of autonomous behaviors, including division. How does this potential for autonomy affect the organization of cellular processes between nuclei? Here we analyze a simplified model of circadian rhythm, a form of cellular oscillator, in a mathematical model of the filamentous fungus\n                    <jats:italic>Neurospora crassa<\/jats:italic>\n                    . Our results highlight a potential role played by mRNA-protein phase separation to keep mRNAs close to the nuclei from which they originate, while allowing proteins to diffuse freely between nuclei. Our modeling shows that syncytism allows for extreme mRNA efficiency\u2014we demonstrate assembly of a robust oscillator with a transcription rate a thousand-fold less than in comparable uninucleate cells. We also show self-organized division of the labor of mRNA production, with one nucleus in a two-nucleus syncytium producing at least twice as many mRNAs as the other in 30% of cycles. This division can occur spontaneously, but division of labor can also be controlled by regulating the amount of cytoplasmic volume available to each nucleus. Taken together, our results show the intriguing richness and potential for emergent organization among nuclei in multinucleate cells. They also highlight the role of previously studied mechanisms of cellular organization, including nuclear space control and localization of mRNAs through RNA-protein phase separation, in regulating nuclear coordination.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008828","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T13:43:16Z","timestamp":1627911796000},"page":"e1008828","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circadian rhythm shows potential for mRNA efficiency and self-organized division of labor in multinucleate cells"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5445-9915","authenticated-orcid":true,"given":"Leif","family":"Zinn-Brooks","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8756-0112","authenticated-orcid":true,"given":"Marcus L.","family":"Roper","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"issue":"6","key":"pcbi.1008828.ref001","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm3118","article-title":"Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis","volume":"12","author":"T Braun","year":"2011","journal-title":"Nat Rev Mol Cell Bio"},{"issue":"3","key":"pcbi.1008828.ref002","first-page":"256","article-title":"Mechanosensation and fluid transport in living bone","volume":"2","author":"S Cowin","year":"2002","journal-title":"J Musculoskel Neuron"},{"issue":"1","key":"pcbi.1008828.ref003","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.devcel.2008.11.003","article-title":"Plasma Membrane Polarity and Compartmentalization are Established Before Cellularization in the Fly Embryo","volume":"16","author":"M Mavrakis","year":"2009","journal-title":"Dev Cell"},{"issue":"18","key":"pcbi.1008828.ref004","doi-asserted-by":"crossref","first-page":"R786","DOI":"10.1016\/j.cub.2011.06.042","article-title":"Nuclear and genome dynamics in multinucleate ascomycete fungi","volume":"21","author":"M Roper","year":"2011","journal-title":"Curr Biol"},{"key":"pcbi.1008828.ref005","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mib.2015.07.001","article-title":"Life as a moving fluid: fate of cytoplasmic macromolecules in dynamic fungal syncytia","volume":"26","author":"M Roper","year":"2015","journal-title":"Curr Opin Microbiol"},{"issue":"2","key":"pcbi.1008828.ref006","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1128\/jb.108.2.705-714.1971","article-title":"Synthesis and some properties of an actin-like nuclear protein in the slime mold Physarum polycephalum","volume":"108","author":"BM Jockusch","year":"1971","journal-title":"J Bacteriol"},{"key":"pcbi.1008828.ref007","volume-title":"Amphibian immunity","author":"LA Rollins-Smith","year":"2012"},{"key":"pcbi.1008828.ref008","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mib.2015.08.009","article-title":"Nuclear autonomy in multinucleate fungi","volume":"28","author":"SE Roberts","year":"2015","journal-title":"Curr Opin Microbiol"},{"issue":"1","key":"pcbi.1008828.ref009","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/79134","article-title":"Circadian rhythm genetics: from flies to mice to humans","volume":"26","author":"K Wager-Smith","year":"2000","journal-title":"Nat Genet"},{"issue":"3","key":"pcbi.1008828.ref010","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.cell.2007.04.015","article-title":"Riding tandem: circadian clocks and the cell cycle","volume":"129","author":"T Hunt","year":"2007","journal-title":"Cell"},{"issue":"5878","key":"pcbi.1008828.ref011","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1126\/science.1158619","article-title":"Integrating circadian timekeeping with cellular physiology","volume":"320","author":"MC Harrisingh","year":"2008","journal-title":"Science"},{"issue":"3","key":"pcbi.1008828.ref012","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.cub.2008.12.042","article-title":"Light-dependent interactions between the Drosophila circadian clock factors cryptochrome, jetlag, and timeless","volume":"19","author":"N Peschel","year":"2009","journal-title":"Curr Biol"},{"issue":"7","key":"pcbi.1008828.ref013","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/j.bpj.2015.01.043","article-title":"Mathematical modeling and validation of glucose compensation of the Neurospora circadian clock","volume":"108","author":"AA Dovzhenok","year":"2015","journal-title":"Biophys J"},{"key":"pcbi.1008828.ref014","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1128\/9781555819583.ch24","volume-title":"The Fungal Kingdom","author":"JC Dunlap","year":"2017"},{"issue":"2","key":"pcbi.1008828.ref015","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0092-8674(00)80566-8","article-title":"Molecular bases for circadian clocks","volume":"96","author":"JC Dunlap","year":"1999","journal-title":"Cell"},{"key":"pcbi.1008828.ref016","first-page":"57","volume-title":"Cold Spring Harbor Symposia on Quantitative Biology","author":"J Dunlap","year":"2007"},{"key":"pcbi.1008828.ref017","first-page":"49","volume-title":"Circadian Rhythms","author":"C Kramer","year":"2007"},{"issue":"3","key":"pcbi.1008828.ref018","doi-asserted-by":"crossref","first-page":"e1002437","DOI":"10.1371\/journal.pcbi.1002437","article-title":"Comprehensive modelling of the Neurospora circadian clock and its temperature compensation","volume":"8","author":"YY Tseng","year":"2012","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"pcbi.1008828.ref019","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.bpj.2018.07.029","article-title":"Modeling reveals a key mechanism for light-dependent phase shifts of Neurospora circadian rhythms","volume":"115","author":"J Bellman","year":"2018","journal-title":"Biophys J"},{"issue":"4","key":"pcbi.1008828.ref020","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1529\/biophysj.104.053975","article-title":"A Model for the Neurospora Circadian Clock","volume":"88","author":"P Fran\u00e7ois","year":"2005","journal-title":"Biophys J"},{"issue":"6","key":"pcbi.1008828.ref021","doi-asserted-by":"crossref","first-page":"062416","DOI":"10.1103\/PhysRevE.97.062416","article-title":"Entrainment of a cellular circadian oscillator by light in the presence of molecular noise","volume":"97","author":"G Wang","year":"2018","journal-title":"Phys Rev E"},{"issue":"25","key":"pcbi.1008828.ref022","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact stochastic simulation of coupled chemical reactions","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"J Phys Chem-US"},{"key":"pcbi.1008828.ref023","article-title":"Cell Biology by the Numbers","author":"R Milo","year":"2015","journal-title":"Garland Science"},{"issue":"13","key":"pcbi.1008828.ref024","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1091\/mbc.E16-02-0129","article-title":"Clustered nuclei maintain autonomy and nucleocytoplasmic ratio control in a syncytium","volume":"27","author":"SE Dundon","year":"2016","journal-title":"Mol Biol Cell"},{"key":"pcbi.1008828.ref025","volume-title":"Spectral Analysis of Signals","author":"P Stoica","year":"2005"},{"issue":"9","key":"pcbi.1008828.ref026","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.bpj.2014.02.039","article-title":"Molecular mechanisms that regulate the coupled period of the mammalian circadian clock","volume":"106","author":"JK Kim","year":"2014","journal-title":"Biophys J"},{"issue":"4","key":"pcbi.1008828.ref027","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1049\/iet-syb.2015.0090","article-title":"Protein sequestration versus Hill-type repression in circadian clock models","volume":"10","author":"JK Kim","year":"2016","journal-title":"IET Syst Biol"},{"issue":"1","key":"pcbi.1008828.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep35828","article-title":"Synchronizing stochastic circadian oscillators in single cells of Neurospora crassa","volume":"6","author":"Z Deng","year":"2016","journal-title":"Sci Rep"},{"issue":"20","key":"pcbi.1008828.ref029","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1016\/j.cub.2013.07.076","article-title":"Nuclear repulsion enables division autonomy in a single cytoplasm","volume":"23","author":"CA Anderson","year":"2013","journal-title":"Curr Biol"},{"issue":"32","key":"pcbi.1008828.ref030","doi-asserted-by":"crossref","first-page":"12875","DOI":"10.1073\/pnas.1220842110","article-title":"Nuclear dynamics in a fungal chimera","volume":"110","author":"M Roper","year":"2013","journal-title":"P Natl Acad Sci USA"},{"issue":"1","key":"pcbi.1008828.ref031","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1574-6976.2011.00288.x","article-title":"The circadian clock of Neurospora crassa","volume":"36","author":"CL Baker","year":"2012","journal-title":"FEMS Microbiology Rev"},{"issue":"3","key":"pcbi.1008828.ref032","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ymeth.2004.08.018","article-title":"The absolute quantification strategy: a general procedure for the quantification of proteins and post-translational modifications","volume":"35","author":"DS Kirkpatrick","year":"2005","journal-title":"Methods"},{"issue":"1","key":"pcbi.1008828.ref033","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s13068-015-0297-9","article-title":"Deletion of homologs of the SREBP pathway results in hyper-production of cellulases in Neurospora crassa and Trichoderma reesei","volume":"8","author":"MC Reilly","year":"2015","journal-title":"Biotechnol Biofuels"},{"issue":"10","key":"pcbi.1008828.ref034","doi-asserted-by":"crossref","first-page":"e1000545","DOI":"10.1371\/journal.pcbi.1000545","article-title":"Invariant distribution of promoter activities in Escherichia coli","volume":"5","author":"A Zaslaver","year":"2009","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"pcbi.1008828.ref035","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1529\/biophysj.104.058388","article-title":"Spontaneous synchronization of coupled circadian oscillators","volume":"89","author":"D Gonze","year":"2005","journal-title":"Biophys J"},{"issue":"11","key":"pcbi.1008828.ref036","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1529\/biophysj.106.094086","article-title":"A molecular model for intercellular synchronization in the mammalian circadian clock","volume":"92","author":"TL To","year":"2007","journal-title":"Biophys J"},{"issue":"4","key":"pcbi.1008828.ref037","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1371\/journal.pcbi.0030068","article-title":"Synchronization-induced rhythmicity of circadian oscillators in the suprachiasmatic nucleus","volume":"3","author":"S Bernard","year":"2007","journal-title":"PLoS Comput Biol"},{"issue":"4","key":"pcbi.1008828.ref038","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1006\/jtbi.2002.3000","article-title":"Intercellular coupling mechanism for synchronized and noise-resistant circadian oscillators","volume":"216","author":"HR Ueda","year":"2002","journal-title":"J Theor Biol"},{"issue":"3","key":"pcbi.1008828.ref039","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2007.02.047","article-title":"Intercellular coupling confers robustness against mutations in the SCN circadian clock network","volume":"129","author":"AC Liu","year":"2007","journal-title":"Cell"},{"issue":"4","key":"pcbi.1008828.ref040","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1073\/pnas.1319399111","article-title":"Circadian rhythms synchronize mitosis in Neurospora crassa","volume":"111","author":"CI Hong","year":"2014","journal-title":"P Natl Acad Sci USA"},{"issue":"34","key":"pcbi.1008828.ref041","doi-asserted-by":"crossref","first-page":"9605","DOI":"10.1073\/pnas.1525268113","article-title":"Circadian clock regulation of mRNA translation through eukaryotic elongation factor eEF-2","volume":"113","author":"SZ Caster","year":"2016","journal-title":"P Natl Acad Sci USA"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008828","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T15:23:58Z","timestamp":1628781838000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008828"}},"subtitle":[],"editor":[{"given":"William","family":"Cannon","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2021,8,2]]},"references-count":41,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008828","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.02.24.432653","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,2]]}}}