Jackson et al. 2018 (PRJNA494404)

General Details

Title	The Translation of Non-Canonical Open Reading Frames Controls Mucosal Immunity
Organism
Number of Samples	4
Release Date	2018/10/02 00:00
Sequencing Types
Protocol Details

Study Links

GWIPS-viz	Trips-Viz

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)
	SRR7956050	PRJNA494404	Mus musculus	NA_Macrophage	Ribo-Seq	Cycloheximide
	SRR7956051	PRJNA494404	Mus musculus	NA_Macrophage	Ribo-Seq	Cycloheximide
	SRR7956052	PRJNA494404	Mus musculus	NA_Macrophage	Ribo-Seq	Cycloheximide
	SRR7956053	PRJNA494404	Mus musculus	NA_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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