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Series GSE67305 Query DataSets for GSE67305
Status Public on Oct 14, 2015
Title Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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. Transcriptome-wide, we discovered extensive rhythms in ribosome occupancy, and identified a core set of ≈150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from non-oscillating 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 re-initiation 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.
 
Overall design A total of 48 mice were entrained under 12hours light:dark conditions for 2 weeks and also collected under 12hours light:dark. Mice were sacrificed every two hours during the 24 hours daily cycle. Two replicates per time point, each replicate is a pool of 2 livers.
 
Contributor(s) Janich P, Arpat AB, Castelo Székély V, Gatfield D
Citation(s) 26486724, 27114907, 28475894
Submission date Mar 26, 2015
Last update date Aug 02, 2019
Contact name David Gatfield
E-mail(s) david.gatfield@unil.ch
Phone +41 21 692 39 94
Organization name University of Lausanne
Department CIG
Street address UNIL CIG
City Lasuanne
ZIP/Postal code 1015
Country Switzerland
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (48)
GSM1644076 RP_ZT0_1; ZT0, ribosome footprint, rep1
GSM1644077 RP_ZT0_2; ZT0, ribosome footprint, rep2
GSM1644078 RP_ZT2_1; ZT2, ribosome footprint, rep1
Relations
BioProject PRJNA279465
SRA SRP056576

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Supplementary file Size Download File type/resource
GSE67305_RAW.tar 6.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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