Mitotic checkpoint gene expression is tuned by codon usage bias

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dc.contributor.authorEsposito, Ericen
dc.contributor.authorWeidemann, Douglas E.en
dc.contributor.authorRogers, Jessie M.en
dc.contributor.authorMorton, Claire M.en
dc.contributor.authorBaybay, Erod Keatonen
dc.contributor.authorChen, Jingen
dc.contributor.authorHauf, Silkeen
dc.date.accessioned2024-02-05T13:04:41Zen
dc.date.available2024-02-05T13:04:41Zen
dc.date.issued2022-08-01en
dc.description.abstractThe mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+, their short mRNA half-lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1+ mRNA has a short half-life despite a higher frequency of optimal codons, and despite the lack of known RNA-destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.en
dc.description.versionPublished versionen
dc.format.extent25 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e107896 (Article number)en
dc.identifier.doihttps://doi.org/10.15252/embj.2021107896en
dc.identifier.eissn1460-2075en
dc.identifier.issn0261-4189en
dc.identifier.issue15en
dc.identifier.orcidHauf, Silke [0000-0001-5938-721X]en
dc.identifier.orcidChen, Jing [0000-0001-6321-0505]en
dc.identifier.pmid35811551en
dc.identifier.urihttps://hdl.handle.net/10919/117848en
dc.identifier.volume41en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/35811551en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectco-translational assemblyen
dc.subjectgene expression noiseen
dc.subjectmitosisen
dc.subjectmRNA decayen
dc.subjectspindle assembly checkpointen
dc.subject.meshKinetochoresen
dc.subject.meshSchizosaccharomycesen
dc.subject.meshCell Cycle Proteinsen
dc.subject.meshSchizosaccharomyces pombe Proteinsen
dc.subject.meshRNA, Messengeren
dc.subject.meshGene Expressionen
dc.subject.meshM Phase Cell Cycle Checkpointsen
dc.subject.meshMad2 Proteinsen
dc.subject.meshSpindle Apparatusen
dc.subject.meshCodon Usageen
dc.titleMitotic checkpoint gene expression is tuned by codon usage biasen
dc.title.serialEMBO Journalen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2022-06-06en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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