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生物
遗传学
基因
基因组
计算生物学
肽序列
作者
Ruaidhrí Jackson,Lina Kroehling,Alexandra Khitun,Will Bailis,Abigail Jarret,Autumn G. York,Omair Khan,J. Richard Brewer,Mathias Skadow,Coco Duizer,Christian C. D. Harman,Lelina Chang,Piotr Bielecki,Ángel G. Alpuche-Solís,Holly R. Steach,Sarah A. Slavoff,Richard A. Flavell
出处
期刊:Nature
[Springer Nature]
日期:2018-12-01
卷期号:564 (7736): 434-438
被引量:151
标识
DOI:10.1038/s41586-018-0794-7
摘要
The annotation of the mammalian protein-coding genome is incomplete. Arbitrary size restriction of open reading frames (ORFs) and the absolute requirement for a methionine codon as the sole initiator of translation have constrained the identification of potentially important transcripts with non-canonical protein-coding potential1,2. Here, using unbiased transcriptomic approaches in macrophages that respond to bacterial infection, we show that ribosomes associate with a large number of RNAs that were previously annotated as 'non-protein coding'. Although the idea that such non-canonical ORFs can encode functional proteins is controversial3,4, we identify a range of short and non-ATG-initiated ORFs that can generate stable and spatially distinct proteins. Notably, we show that the translation of a new ORF 'hidden' within the long non-coding RNA Aw112010 is essential for the orchestration of mucosal immunity during both bacterial infection and colitis. This work expands our interpretation of the protein-coding genome and demonstrates that proteinaceous products generated from non-canonical ORFs are crucial for the immune response in vivo. We therefore propose that the misannotation of non-canonical ORF-containing genes as non-coding RNAs may obscure the essential role of a multitude of previously undiscovered protein-coding genes in immunity and disease.
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