Richard Flavell and colleagues use a ribosome enrichment method in the context of bacterial infection and inflammatory disease to identify non-canonical open reading frames (ORFs) previously identified as non-coding RNAs. They identify numerous new short and non-ATG-initiated ORFs in mouse macrophages that can generate proteins. One of the ORFs is shown to be essential for host immunity to enteric mucosal infection. The authors predict that future evaluation of the human protein-encoding genome may lead to the identification of cryptic non-canonical ORF protein products that may have major implications for human health and disease.
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