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Translation initiation by cap‐dependent ribosome recruitment: Recent insights and open questions

Shirokikh, Nikolay; Preiss, Thomas

Description

Gene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple...[Show more]

dc.contributor.authorShirokikh, Nikolay
dc.contributor.authorPreiss, Thomas
dc.date.accessioned2021-03-16T23:54:37Z
dc.identifier.citationShirokikh NE, Preiss T. Translation initiation by cap-dependent ribosome recruitment: Recent insights and open questions. WIREs RNA. 2018;9:e1473. https://doi.org/10.1002/wrna.1473
dc.identifier.issn1757-7004
dc.identifier.urihttp://hdl.handle.net/1885/227216
dc.description.abstractGene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple types of regulatory intervention. The “consensus” model, featuring cap‐dependent ribosome entry and scanning of mRNA leader sequences, represents the predominantly utilized initiation pathway across eukaryotes, although several variations of the model and alternative initiation mechanisms are also known. Recent advances in structural biology techniques have enabled remarkable molecular‐level insights into the functional states of eukaryotic ribosomes, including a range of ribosomal complexes with different combinations of translation initiation factors that are thought to represent bona fide intermediates of the initiation process. Similarly, high‐throughput sequencing‐based ribosome profiling or “footprinting” approaches have allowed much progress in understanding the elongation phase of translation, and variants of them are beginning to reveal the remaining mysteries of initiation, as well as aspects of translation termination and ribosomal recycling. A current view on the eukaryotic initiation mechanism is presented here with an emphasis on how recent structural and footprinting results underpin axioms of the consensus model. Along the way, we further outline some contested mechanistic issues and major open questions still to be addressed.
dc.description.sponsorshipThe work was supported by Australian Research Council grant DP130101928 and Cancer Council ACT grant GNT1120469 awarded to Thomas Preiss.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherJohn Wiley & Sons Ltd.
dc.rights© 2018 Wiley Periodicals, Inc.
dc.sourceWiley Interdisciplinary Reviews: RNA
dc.subjecteukaryotic translation initiation
dc.subjectmRNA translation
dc.subjectpost-transcriptional gene regulation
dc.subjectprotein synthesis
dc.subjectribosome
dc.subjectscanning
dc.subjectstart codon recognition
dc.titleTranslation initiation by cap‐dependent ribosome recruitment: Recent insights and open questions
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume9
dcterms.dateAccepted2018-02-14
dc.date.issued2018-04-06
local.identifier.absfor060405 - Gene Expression (incl. Microarray and other genome-wide approaches)
local.identifier.ariespublicationu5786633xPUB249
local.publisher.urlhttps://onlinelibrary.wiley.com/
local.type.statusAccepted Version
local.contributor.affiliationShirokikh, Nikolay, College of Health and Medicine, ANU
local.contributor.affiliationPreiss, Thomas, College of Health and Medicine, ANU
dc.relationhttp://purl.org/au-research/grants/arc/DP130101928
local.bibliographicCitation.issue4
local.bibliographicCitation.startpage1
local.bibliographicCitation.lastpage45
local.identifier.doi10.1002/wrna.1473
dc.date.updated2020-11-23T12:00:22Z
local.identifier.scopusID2-s2.0-85044940952
dcterms.accessRightsOpen Access
dc.provenancehttps://v2.sherpa.ac.uk/id/publication/7587..."Author accepted manuscript can be made open access on non-commercial institutional repository after 12 month embargo" from SHERPA/RoMEO site (as at 18.3.2021).
CollectionsANU Research Publications

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