Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity

Show simple item record

dc.contributor.author Ivanov, Ivaylo P.
dc.contributor.author Wei, Jiajie
dc.contributor.author Caster, Stephen Z.
dc.contributor.author Smith, Kristina M.
dc.contributor.author Michel, Audrey M.
dc.contributor.author Zhang, Ying
dc.contributor.author Firth, Andrew E.
dc.contributor.author Freitag, Michael
dc.contributor.author Dunlap, Jay C.
dc.contributor.author Bell-Pedersen, Deborah
dc.contributor.author Atkins, John F.
dc.contributor.author Sachs, Matthew S.
dc.date.accessioned 2017-09-26T11:39:19Z
dc.date.available 2017-09-26T11:39:19Z
dc.date.issued 2017
dc.identifier.citation Ivanov, I. P., Wei, J., Caster, S. Z., Smith, K. M., Michel, A. M., Zhang, Y., Firth, A. E., Freitag, M., Dunlap, J. C., Bell-Pedersen, D., Atkins, J. F. and Sachs, M. S. (2017) 'Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity', mBio, 8(3). e00844-17 (17pp). doi: 10.1128/mBio.00844-17 en
dc.identifier.volume 8
dc.identifier.issued 3
dc.identifier.issn 2150-7511
dc.identifier.uri http://hdl.handle.net/10468/4788
dc.identifier.doi 10.1128/mBio.00844-17
dc.description.abstract Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700-nucleotide (nt) 5' leader, and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4, respectively, in controlling translation. We also found that the 5' region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5' conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscores the emerging significance of noncanonical initiation events in controlling gene expression. IMPORTANCE There is a deepening and widening appreciation of the diverse roles of translation in controlling gene expression. A central fungal transcription factor, the best-studied example of which is Saccharomyces cerevisiae GCN4, is crucial for the response to amino acid limitation. Two upstream open reading frames (uORFs) in the GCN4 mRNA are critical for controlling GCN4 synthesis. We observed that two uORFs in the corresponding Neurospora crassa cpc-1 mRNA appear functionally analogous to the GCN4 uORFs. We also discovered that, surprisingly, unlike GCN4, the CPC1 coding sequence extends far upstream from the presumed AUG start codon with no other in-frame AUG codons. Similar extensions were seen in homologs from many filamentous fungi. We observed that multiple non-AUG near-cognate codons (NCCs) in this extended reading frame, some conserved, initiated translation to produce longer forms of CPC1, underscoring the significance of noncanonical initiation in controlling gene expression. en
dc.description.sponsorship National Institutes of Health (GM068087, GM47498) Wellcome Trust (106207) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher American Society for Microbiology en
dc.relation.uri http://mbio.asm.org/content/8/3/e00844-17
dc.rights © 2017, Ivanov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Neurospora en
dc.subject Filamentous fungi en
dc.subject Gene regulation en
dc.subject Molecular genetics en
dc.subject Translational control en
dc.subject Messengerrna translation en
dc.subject Aminoacid biosynthesis en
dc.subject Factor 1 eIF1 en
dc.subject Neurosporacrassa en
dc.subject Mammaliancells en
dc.subject In vivo en
dc.subject Modulates autoregulation en
dc.subject Nucleotide resolution en
dc.subject Functional elements en
dc.subject Ribosome binding en
dc.title Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Ivaylo P. Ivanov, Biochemistry and Cell Biology, University College Cork, Cork, Ireland +353-21-490-3000. Email: 116224625@umail.ucc.ie en
dc.internal.authorcontactother John F. Atkins, Biochemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: j.atkins@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.rssid 431799813
dc.internal.wokid WOS:000404733300068
dc.contributor.funder Texas A and M University
dc.contributor.funder Wellcome Trust
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder National Institutes of Health
dc.description.status Peer reviewed en
dc.identifier.journaltitle mBio en
dc.internal.IRISemailaddress 116224625@umail.ucc.ie en
dc.internal.IRISemailaddress j.atkins@ucc.ie en
dc.identifier.articleid e00844-17
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Principal Investigator Programme (PI)/08/IN.1/B1889/IE/Altered Genetic Code Readout/


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 2017, Ivanov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Except where otherwise noted, this item's license is described as © 2017, Ivanov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement