AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.

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dc.contributor.authorYordanova, Martina M.
dc.contributor.authorLoughran, Gary
dc.contributor.authorZhdanov, Alexander V.
dc.contributor.authorMariotti, Marco
dc.contributor.authorKiniry, Stephen J.
dc.contributor.authorO'Connor, Patrick B. F.
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorTzani, Ioanna
dc.contributor.authorSaffert, Paul
dc.contributor.authorMichel, Audrey M.
dc.contributor.authorGladyshev, Vadim N.
dc.contributor.authorPapkovsky, Dmitri B.
dc.contributor.authorAtkins, John F.
dc.contributor.authorBaranov, Pavel V.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderRussian Science Foundationen
dc.contributor.funderHealth Research Boarden
dc.date.accessioned2018-02-14T15:40:04Z
dc.date.available2018-02-14T15:40:04Z
dc.date.issued2018-01-03
dc.date.updated2018-02-14T15:30:27Z
dc.description.abstractIn addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process1,2. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage.en
dc.description.sponsorshipHealth Research Board (PhD/2007/04); Russian Science Foundation (16-14-10065)en
dc.description.statusPeer revieweden
dc.description.versionSubmitted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationYordanova, M. M., Loughran, G., Zhdanov, A. V., Mariotti, M., Kiniry, S. J., O’Connor, P. B. F., Andreev, D. E., Tzani, I., Saffert, P., Michel, A. M., Gladyshev, V. N., Papkovsky, D. B., Atkins, J. F. and Baranov, P. V. (2018) 'AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation', Nature, 553, pp. 356. doi: 10.1038/nature25174en
dc.identifier.doi10.1038/nature25174
dc.identifier.endpage360en
dc.identifier.issn1476-4687
dc.identifier.journaltitleNatureen
dc.identifier.startpage356en
dc.identifier.urihttps://hdl.handle.net/10468/5463
dc.identifier.volume553en
dc.language.isoenen
dc.publisherMacmillan Publishers Ltd, part of Springer Natureen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1335/IE/Development of computational resources for the analysis of Genome Wide Information on Protein Synthesis (GWIPS)./en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/en
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2276/IE/I-PIC Irish Photonic Integration Research Centre/en
dc.relation.projectinfo:eu-repo/grantAgreement/NIH/NATIONAL CANCER INSTITUTE/5R01CA080946-07/US/Selenoproteins as Targets for Cancer Prevention/en
dc.relation.projectinfo:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES/1R01GM065204-01/US/Functions of Mammalian thioredoxin reductases/en
dc.rights© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.en
dc.subjectGene regulationen
dc.subjectTranslationen
dc.subjectProtein synthesisen
dc.subjectMessenger RNAen
dc.subjectmRNAen
dc.titleAMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.en
dc.typeArticle (peer-reviewed)en
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