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

• 藤田, 祥彦

• 齊藤, 博英

• Wan, Ji

• Moore, Chelsea

• Fujita, Yoshihiko

• 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

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.

収録刊行物

• Nucleic Acids Research

  Nucleic Acids Research 45 (20), 11941-11953, 2017-11-16

  Oxford University Press (OUP)

キーワード

• Genetics

詳細情報

• CRID: 1050282813184527360
• NII論文ID: 120006537139
• ISSN: 03051048
• ISSN: 13624962
• DOI: 10.1093/nar/gkx808
• HANDLE: 2433/235158
• Web Site: http://academic.oup.com/nar/article-pdf/45/20/11941/21743147/gkx808.pdf
• 本文言語コード: en
• 資料種別: journal article
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