The translation of non-canonical open reading frames controls mucosal immunity

Ruaidhrí Jackson, Lina Kroehling, Alexandra Khitun, Will Bailis, Abigail Jarret, Autumn G. York, Omair M. Khan, J. Richard Brewer, Mathias H. Skadow, Coco Duizer, Christian C. D. Harman, Lelina Chang, Piotr Bielecki, Angel G. Solis, Holly R. Steach, Sarah Slavoff and Richard A. Flavell ()
Additional contact information
Ruaidhrí Jackson: Yale University School of Medicine
Lina Kroehling: Yale University School of Medicine
Alexandra Khitun: Yale University
Will Bailis: Yale University School of Medicine
Abigail Jarret: Yale University School of Medicine
Autumn G. York: Yale University School of Medicine
Omair M. Khan: Yale University School of Medicine
J. Richard Brewer: Yale University School of Medicine
Mathias H. Skadow: Yale University School of Medicine
Coco Duizer: Yale University School of Medicine
Christian C. D. Harman: Yale University School of Medicine
Lelina Chang: Yale University School of Medicine
Piotr Bielecki: Yale University School of Medicine
Angel G. Solis: Yale University School of Medicine
Holly R. Steach: Yale University School of Medicine
Sarah Slavoff: Yale University
Richard A. Flavell: Yale University School of Medicine

Nature, 2018, vol. 564, issue 7736, 434-438

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0794-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:564:y:2018:i:7736:d:10.1038_s41586-018-0794-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0794-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().