Genome-wide identification of Arabidopsis non-AUG-initiated upstream ORFs with evolutionarily conserved regulatory sequences that control protein expression levels.
Arabidopsis
Nascent peptide
Non-AUG translation initiation
Translational regulation
Upstream ORF
Journal
Plant molecular biology
ISSN: 1573-5028
Titre abrégé: Plant Mol Biol
Pays: Netherlands
ID NLM: 9106343
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
received:
11
02
2022
accepted:
11
08
2022
pubmed:
1
9
2022
medline:
21
1
2023
entrez:
31
8
2022
Statut:
ppublish
Résumé
This study identified four novel regulatory non-AUG-initiated upstream ORFs (uORFs) with evolutionarily conserved sequences in Arabidopsis and elucidated the mechanism by which a non-AUG-initiated uORF promotes main ORF translation. Upstream open reading frames (uORFs) are short ORFs found in the 5'-untranslated regions (5'-UTRs) of eukaryotic transcripts and can influence the translation of protein-coding main ORFs (mORFs). Recent genome-wide ribosome profiling studies have revealed that hundreds or thousands of uORFs initiate translation at non-AUG start codons. However, the physiological significance of these non-AUG uORFs has so far been demonstrated for only a few of them. In this study, to identify physiologically important regulatory non-AUG uORFs in Arabidopsis, we took an approach that combined bioinformatics and experimental analysis. Since physiologically important non-AUG uORFs are likely to be conserved across species, we first searched the Arabidopsis genome for non-AUG-initiated uORFs with evolutionarily conserved sequences. Then, we examined the effects of the conserved non-AUG uORFs on the expression of the downstream mORFs using transient expression assays. As a result, three inhibitory and one promotive non-AUG uORFs were identified. Among the inhibitory non-AUG uORFs, two exerted repressive effects on mORF expression in an amino acid sequence-dependent manner. These two non-AUG uORFs are likely to encode regulatory peptides that cause ribosome stalling, thereby enhancing their repressive effects. In contrast, one of the identified regulatory non-AUG uORFs promoted mORF expression by alleviating the inhibitory effect of a downstream AUG-initiated uORF. These findings provide insights into the mechanisms that enable non-AUG uORFs to play regulatory roles despite their low translation initiation efficiencies.
Identifiants
pubmed: 36044152
doi: 10.1007/s11103-022-01309-1
pii: 10.1007/s11103-022-01309-1
doi:
Substances chimiques
Codon, Initiator
0
5' Untranslated Regions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
37-55Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP19K22299
Organisme : Japan Society for the Promotion of Science
ID : JP16H05063
Organisme : Japan Society for the Promotion of Science
ID : JP20H0592
Organisme : Japan Society for the Promotion of Science
ID : JP19H02917
Organisme : Japan Society for the Promotion of Science
ID : 21K15114
Organisme : Japan Society for the Promotion of Science
ID : JP19K16159
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.
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