Dataset Information

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver.

ABSTRACT: In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of RNA accumulation and affecting the distribution of transcripts in different subcellular compartments. Our study analysed the nuclear and cytoplasmic, poly(A) and total transcriptomes of mouse livers collected over the course of a day. These data provide a genome-wide temporal inventory of enrichment in subcellular RNA, and revealed specific signatures of splicing, nuclear export and cytoplasmic mRNA stability related to transcript and gene lengths. Combined with a mathematical model describing rhythmic RNA profiles, we could test the rhythmicity of export rates and cytoplasmic degradation rates of approximately 1400 genes. With nuclear export times usually much shorter than cytoplasmic half-lives, we found that nuclear export contributes to the modulation and generation of rhythmic profiles of 10% of the cycling nuclear mRNAs. This study contributes to a better understanding of the dynamic regulation of the transcriptome during the day-night cycle.

SUBMITTER: Hurni C

PROVIDER: S-EPMC9377612 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver.

Hurni Clémence C Weger Benjamin D BD Gobet Cédric C Naef Felix F

PLoS genetics 20220803 8

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of RNA accumulation and affecting the distribution of transcripts in different subcellular compartments. Our study analysed the nuclear and cytoplasmic, poly(A) and total transcriptomes of mouse livers collected over the course of a day. These dat ...[more]

PMID: 35921362

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Project description:The presence of a phagocytic peak of photoreceptor outer segments by the retinal pigment epithelium (RPE) one or 2 h after the onset of light has been reported for several diurnal and nocturnal species. This peak in phagocytic activity also persists under constant lighting conditions (i.e., constant light or dark) thus demonstrating that the timing of this peak is driven by a circadian clock. The aim of this study was to investigate the change in RPE whole transcriptome at two different circadian times (CT; 1 h before (CT23) and 1 h after (CT1) subjective light onset). C57BL/6J male mice were maintained in constant dark conditions for three days and euthanized under red light (<1 lux) at CT23 and CT1. RPE was isolated from whole eyes for RNA library preparation and sequencing on an Illumina HiSeq4000 platform. 14,083 mouse RPE transcripts were detected in common between CT23 and CT1. 12,005 were protein coding transcripts and 2078 were non-protein coding transcripts. 2421 protein coding transcripts were significantly upregulated whereas only 3 transcripts were significantly downregulated and 12 non-protein coding transcripts were significantly upregulated and 31 non-protein coding transcripts were significantly downregulated at CT1 when compared to CT23 (p < 0.05, fold change ≥ ±2.0). Of the protein coding transcripts, most of them were characterized as: enzymes, kinases, and transcriptional regulators with a large majority of activity in the cytoplasm, nucleus, and plasma membrane. Non-protein coding transcripts included biotypes such as long-non coding RNAs and pseudogenes. Gene ontology analysis and ingenuity pathway analysis revealed that differentially expressed transcripts were associated with integrin signaling, oxidative phosphorylation, protein phosphorylation, and actin cytoskeleton remodeling suggesting that these previously identified phagocytic pathways are under circadian control. Our analysis identified new pathways (e.g., increased mitochondrial respiration via increased oxidative phosphorylation) that may be involved in the circadian control of phagocytic activity. In addition, our dataset suggests a possible regulatory role for the identified non-protein coding transcripts in mediating the complex function of RPE phagocytosis. Finally, our results also indicate, as seen in other tissues, about 20% of the whole RPE transcriptome may be under circadian clock regulation.

Project description:The circadian clock is an evolutionary system that allows organisms to anticipate and thus adapt to daily changes in the environment. In mammals, the circadian clock is found in virtually every tissue regulating rhythms of metabolism and physiology. While a lot of studies have focused in how circadian clocks regulate gene expression little is known about daily control of protein abundance. Here we applied state of the art mass spectrometry in combination with quantitative proteomics to investigate global circadian oscillations of the proteome in the mouse liver. We found that approximately 6% of the liver proteins are cycling daily and interestingly the majority of these oscillations diverge from the behavior of their transcripts. Our data indicates that post-transcriptional mechanisms play an essential role in shaping the phase of rhythmic proteins downstream of transcription regulation to ultimately drive rhythms of metabolism. Moreover, the contribution of post-transcriptional regulation seems to differ among distinct metabolic pathways. Overall we not only found circadian oscillations in the abundance of proteins involved in liver specific metabolic pathways but also in essential cellular processes. Data processing: Raw MS files were processed with MaxQuant (version. 1.1.1.9), a freely available software suite. Peak list files were searched by the ANDROMEDA a search engine, incorporated into the MaxQuant framework, against the IPI-mouse (version 3.68) containing both forward and reversed protein sequences. Initial maximum precursor and fragment mass deviations were set to 7 ppm and 0.5 Da, respectively, but MaxQuant achieved sub-ppm mass accuracy for the majority of peptide precursors. The search included variable modifications for oxidation of methionine, protein N-terminal acetylation and carbamidomethylation as fixed modification. Peptides with at least six amino acids were considered for identification specifying as enzyme LysC allowing N-terminal cleavage to proline. The false discovery rate, determined by searching a reverse database, was set at 0.01 for both peptides and proteins. Identification across different replicates and adjacent fractions was achieved by enabling matching between runs option in MaxQuant within a time window of 2 minutes. Quantification of SILAC pairs was performed by MaxQuant with standard settings using a minimum ratio count of 2.

Dataset Information

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver.

Publications

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver.

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