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タイトル: | Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide |
著者: | Tang, Leiming Morris, Jacob Wan, Ji Moore, Chelsea Fujita, Yoshihiko https://orcid.org/0000-0001-6321-2121 (unconfirmed) Gillaspie, Sarah Aube, Eric Nanda, Jagpreet Marques, Maud Jangal, Maika Anderson, Abbey Cox, Christian Hiraishi, Hiroyuki Dong, Leiming Saito, Hirohide Singh, Chingakham Ranjit Witcher, Michael Topisirovic, Ivan Qian, Shu-Bing Asano, Katsura |
著者名の別形: | 藤田, 祥彦 齊藤, 博英 |
発行日: | 16-Nov-2017 |
出版者: | Oxford University Press (OUP) |
誌名: | Nucleic Acids Research |
巻: | 45 |
号: | 20 |
開始ページ: | 11941 |
終了ページ: | 11953 |
抄録: | In the human genome, translation initiation from non-AUG 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, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP. |
著作権等: | © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com. |
URI: | http://hdl.handle.net/2433/235158 |
DOI(出版社版): | 10.1093/nar/gkx808 |
PubMed ID: | 28981728 |
出現コレクション: | 学術雑誌掲載論文等 |
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