Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames.

Détails

Ressource 1Télécharger: BIB_5CC6939B3A97.P001.pdf (4613.70 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_5CC6939B3A97
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames.
Périodique
Genome Research
Auteur(s)
Janich P., Arpat A.B., Castelo-Szekely V., Lopes M., Gatfield D.
ISSN
1549-5469 (Electronic)
ISSN-L
1088-9051
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
25
Numéro
12
Pages
1848-1859
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.
Mots-clé
5' Untranslated Regions, Animals, Biomarkers, Circadian Clocks/genetics, Circadian Rhythm/genetics, Computational Biology/methods, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, High-Throughput Nucleotide Sequencing, Liver/metabolism, Male, Mice, Open Reading Frames, Protein Biosynthesis, RNA, Messenger/genetics, RNA, Messenger/metabolism, Response Elements, Ribosomes/genetics, Ribosomes/metabolism, Transcriptome
Pubmed
Web of science
Open Access
Oui
Création de la notice
16/10/2015 8:45
Dernière modification de la notice
20/08/2019 15:15
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