| First Author | Jackson R | Year | 2018 |
| Journal | Nature | Volume | 564 |
| Issue | 7736 | Pages | 434-438 |
| PubMed ID | 30542152 | Mgi Jnum | J:267975 |
| Mgi Id | MGI:6268460 | Doi | 10.1038/s41586-018-0794-7 |
| Citation | Jackson R, et al. (2018) The translation of non-canonical open reading frames controls mucosal immunity. Nature 564(7736):434-438 |
| abstractText | 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(1,2). 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 controversial(3,4), 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. |
