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

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dc.contributor.author Yordanova, Martina M.
dc.contributor.author Loughran, Gary
dc.contributor.author Zhdanov, Alexander V.
dc.contributor.author Mariotti, Marco
dc.contributor.author Kiniry, Stephen J.
dc.contributor.author O'Connor, Patrick B. F.
dc.contributor.author Andreev, Dmitry E.
dc.contributor.author Tzani, Ioanna
dc.contributor.author Saffert, Paul
dc.contributor.author Michel, Audrey M.
dc.contributor.author Gladyshev, Vadim N.
dc.contributor.author Papkovsky, Dmitri B.
dc.contributor.author Atkins, John F.
dc.contributor.author Baranov, Pavel V.
dc.date.accessioned 2018-02-14T15:40:04Z
dc.date.available 2018-02-14T15:40:04Z
dc.date.issued 2018-01-03
dc.identifier.citation Yordanova, 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/nature25174 en
dc.identifier.volume 553 en
dc.identifier.startpage 356 en
dc.identifier.endpage 360 en
dc.identifier.issn 1476-4687
dc.identifier.uri http://hdl.handle.net/10468/5463
dc.identifier.doi 10.1038/nature25174
dc.description.abstract In 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.sponsorship Health Research Board (PhD/2007/04); Russian Science Foundation (16-14-10065) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Macmillan Publishers Ltd, part of Springer Nature en
dc.rights © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. en
dc.subject Gene regulation en
dc.subject Translation en
dc.subject Protein synthesis en
dc.subject Messenger RNA en
dc.subject mRNA en
dc.title AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation. en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Pavel Baranov, School Of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: p.baranov@ucc.ie en
dc.internal.availability Full text available en
dc.date.updated 2018-02-14T15:30:27Z
dc.description.version Submitted Version en
dc.internal.rssid 421919545
dc.internal.pmid 29310120
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder National Institutes of Health en
dc.contributor.funder Russian Science Foundation en
dc.contributor.funder Health Research Board en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Nature en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress p.baranov@ucc.ie en
dc.relation.project info: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.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/13/IA/1853/IE/Dynamic redefinition of codons: From antivirals to an essential micronutrient/ en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2276/IE/I-PIC Irish Photonic Integration Research Centre/ en
dc.relation.project info:eu-repo/grantAgreement/NIH/NATIONAL CANCER INSTITUTE/5R01CA080946-07/US/Selenoproteins as Targets for Cancer Prevention/ en
dc.relation.project info:eu-repo/grantAgreement/NIH/NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES/1R01GM065204-01/US/Functions of Mammalian thioredoxin reductases/ en


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