title: Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.
abstract: Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.
authors.affiliation: Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; Department of Pharmacology and Toxicology, University of Lausanne, CH-1011 Lausanne, Switzerland;
authors.forename: Florian
authors.initials: F
authors.lastname: Atger
authors.affiliation: Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland;
authors.forename: Cédric
authors.initials: C
authors.lastname: Gobet
authors.affiliation: Functional Genomic, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland;
authors.forename: Julien
authors.initials: J
authors.lastname: Marquis
authors.affiliation: Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland;
authors.forename: Eva
authors.initials: E
authors.lastname: Martin
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland;
authors.forename: Jingkui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weger
authors.affiliation: Functional Genomic, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland;
authors.forename: Grégory
authors.initials: G
authors.lastname: Lefebvre
authors.affiliation: Functional Genomic, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland; felix.naef@epfl.ch frederic.gachon@rd.nestle.com.
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
authors.affiliation: Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland; Faculty of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland felix.naef@epfl.ch frederic.gachon@rd.nestle.com.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gachon
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D056930:ARNTL Transcription Factors / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D005247:Feeding Behavior; D017353:Gene Deletion; D000076222:Mechanistic Target of Rapamycin Complex 1; D018345:Mice, Knockout; D008957:Models, Genetic; D046912:Multiprotein Complexes; D059372:Nucleotide Motifs / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012270:Ribosomes / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase
keywords: 5′-TOP sequences; TISU motifs; circadian rhythms; mRNA translation; ribosome profiling