Jackson et al. 2018 (PRJNA494404)

General Details

Title The Translation of Non-Canonical Open Reading Frames Controls Mucosal Immunity
Organism
Number of Samples 10
Release Date 2018/10/02 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP163147
ENA SRP163147
GEO GSE120762
BioProject PRJNA494404

Publication

Title
Authors Jackson R,Kroehling L,Khitun A,Bailis W,Jarret A,York AG,Khan OM,Brewer JR,Skadow MH,Duizer C,Harman CCD,Chang L,Bielecki P,Solis AG,Steach HR,Slavoff S,Flavell RA
Journal Nature
Publication Date 2018 Dec
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 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.
PMC PMC6939389
PMID 30542152
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR7956044 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956045 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956046 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956047 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956048 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956049 PRJNA494404 Mus musculus Macrophage RiboTag
SRR7956050 PRJNA494404 Mus musculus Macrophage Ribo-Seq Cycloheximide
SRR7956051 PRJNA494404 Mus musculus Macrophage Ribo-Seq Cycloheximide
SRR7956052 PRJNA494404 Mus musculus Macrophage Ribo-Seq Cycloheximide
SRR7956053 PRJNA494404 Mus musculus Macrophage Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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