Nature (London), 2018-12, Vol.564 (7736), p.434-438
2018
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- The translation of non-canonical open reading frames controls mucosal immunity
- Ist Teil von
- Nature (London), 2018-12, Vol.564 (7736), p.434-438
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 potential . 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 controversial , 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-018-0794-7Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6939389
- Format
- –
- Schlagworte
- Animals, Annotations, B cells, Bacterial infections, Bacterial Infections - genetics, Bacterial Infections - immunology, Bacterial Infections - metabolism, Bacterial Infections - microbiology, Bioinformatics, Codons, Colitis, Colitis - genetics, Colitis - immunology, Colitis - metabolism, Gene expression, Genes, Genomes, Genomics, Immune response, Immune system, Immunity, Immunity, Mucosal - drug effects, Immunity, Mucosal - genetics, Infection, Infections, Inflammation, Inflammatory bowel disease, Interleukin-12 - biosynthesis, Lipopolysaccharides - pharmacology, Macrophages, Macrophages - immunology, Macrophages - metabolism, Methionine, Mice, Mucosal immunity, Mucous membrane, Non-coding RNA, Open reading frames, Open Reading Frames - genetics, Peptides, Physiological aspects, Protein Biosynthesis - drug effects, Protein Biosynthesis - genetics, Proteins, Resveratrol, Ribonucleic acid, Ribosomes, Ribosomes - drug effects, Ribosomes - metabolism, RNA, RNA, Long Noncoding - genetics, RNA, Long Noncoding - metabolism, Salmonella, Salmonella typhimurium - immunology, Transcriptome - drug effects, Transcriptome - genetics, Translation