Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide

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dc.contributor.author Tang, Leiming
dc.contributor.author Morris, Jacob
dc.contributor.author Wan, Ji
dc.contributor.author Moore, Chelsea
dc.contributor.author Fujita, Yoshihiko
dc.contributor.author Gillaspie, Sarah
dc.contributor.author Aube, Eric
dc.contributor.author Nanda, Jagpreet
dc.contributor.author Marques, Maud
dc.contributor.author Jangal, Maika
dc.contributor.author Anderson, Abbey
dc.contributor.author Cox, Christian
dc.contributor.author Hiraishi, Hiroyuki
dc.contributor.author Dong, Leiming
dc.contributor.author Saito, Hirohide
dc.contributor.author Singh, Chingakham Ranjit
dc.contributor.author Witcher, Michael
dc.contributor.author Topisirovic, Ivan
dc.contributor.author Qian, Shu-Bing
dc.contributor.author Asano, Katsura
dc.date.accessioned 2018-11-13T17:11:15Z
dc.date.available 2018-11-13T17:11:15Z
dc.date.issued 2017-11-16
dc.identifier.uri http://hdl.handle.net/2097/39257
dc.description Citation: Tang, L., Morris, J., Wan, J., Moore, C., Fujita, Y., Gillaspie, S., … Asano, K. (2017). Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide. Nucleic Acids Research, 45(20), 11941–11953. https://doi.org/10.1093/nar/gkx808
dc.description.abstract In the human genome, translation initiation from nonAUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUGinitiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP.
dc.relation.uri https://doi.org/10.1093/nar/gkx808
dc.rights Attribution 4.0 International (CC BY 4.0)
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide
dc.type Text
dc.date.published 2017
dc.citation.doi 10.1093/nar/gkx808
dc.citation.issn 0305-1048, 1362-4962
dc.citation.issue 20
dc.citation.jtitle Nucleic Acids Research
dc.citation.volume 45
dc.citation Tang, L., Morris, J., Wan, J., Moore, C., Fujita, Y., Gillaspie, S., … Asano, K. (2017). Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide. Nucleic Acids Research, 45(20), 11941–11953. https://doi.org/10.1093/nar/gkx808
dc.description.version Article:Version of Record (VOR)


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