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Diurnal oscillations in human salivary microRNA and microbial transcription

ABSTRACT: Diurnal oscillations in human salivary microRNA and microbial transcription

PROVIDER: PRJNA479866 | ENA |

REPOSITORIES: ENA

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Diurnal oscillations in human salivary microRNA and microbial transcription

Project description:We investigated daily oscillations in salivary miRNA and microbial RNA to explore relationships between these components of the gut-brain-axis and their implications in human health. Nine subjects provided 120 saliva samples at designated times, on repeated days. Samples were divided into three sets for exploration and cross-validation. Identification and quantification of host miRNA and microbial RNA was performed using next generation sequencing. Eleven miRNAs and 11 microbial RNAs demonstrated consistent diurnal oscillation across the first 2 sample sets and accurately predicted collection time in the hold-out set based on multivariate logistic regression modeling. Associations among five circadian miRNAs and four circadian microbial RNAs were observed.

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The role of PER1/2 and feeding rhythms in daily oscillations of mitochondrial nutrient utilization and rate-limiting enzymes

Project description:Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied mass-spectrometry based quantitative proteomics on isolated mitochondria from mice sacrificed throughout the day and identified extensive oscillations in the mitochondrial proteome. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or upon nutritional challenge such as high fat diet. We propose that the clock proteins PER1/2 optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby serve as a rheostat for mitochondrial nutrient utilization.

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Angiopoietin-like 4 governs diurnal lipoprotein lipase activity in brown adipose tissue.

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Dampening of expression oscillations by synchronous regulation of a microRNA and its target

Project description:The complexity of metazoan organisms requires precise spatiotemporal regulation of gene expression during development. To identify different modes of developmental gene regulation we measured the transcriptome throughout development of the nematode Caenorhabditis elegans by mRNA sequencing with high temporal resolution. We find that approximately 2,000 transcripts undergo expression oscillations synchronized with larval transitions while thousands of genes are expressed in temporal gradients, similar to known timing regulators. By counting transcripts in individual animals, we show that the pulsatile expression of the microRNA (miRNA) lin-4 maintains the temporal gradient of its target lin-14 by dampening its expression oscillations. Our results demonstrate that this insulation is optimal when pulsatile expression of the miRNA and its target is synchronous. We propose that such a miRNA-mediated incoherent feed-forward loop is a potent filter that prevents propagation of potentially deleterious gene expression fluctuations during the development of an organism.

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