Journal of Biological Chemistry
Volume 290, Issue 39, 25 September 2015, Pages 23680-23691
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RNA
Uptake and Function Studies of Maternal Milk-derived MicroRNAs*

https://doi.org/10.1074/jbc.M115.676734Get rights and content
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MicroRNAs (miRNAs) are important regulators of cell-autonomous gene expression that influence many biological processes. They are also released from cells and are present in virtually all body fluids, including blood, urine, saliva, sweat, and milk. The functional role of nutritionally obtained extracellular miRNAs is controversial, and irrefutable demonstration of exogenous miRNA uptake by cells and canonical miRNA function is still lacking. Here we show that miRNAs are present at high levels in the milk of lactating mice. To investigate intestinal uptake of miRNAs in newborn mice, we employed genetic models in which newborn miR-375 and miR-200c/141 knockout mice received milk from wild-type foster mothers. Analysis of the intestinal epithelium, blood, liver, and spleen revealed no evidence for miRNA uptake. miR-375 levels in hepatocytes were at the limit of detection and remained orders of magnitude below the threshold for target gene regulation (between 1000 and 10,000 copies/cell). Furthermore, our study revealed rapid degradation of milk miRNAs in intestinal fluid. Together, our results indicate a nutritional rather than gene-regulatory role of miRNAs in the milk of newborn mice.

gene expression
intestine
mammary gland
microRNA (miRNA)
nutrition
absorption
milk

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The small RNA sequencing data reported in this paper have been submitted to the Gene Expression Omnibus Repository with accession number GSE70201.

*

This work was supported by an Excellence and Opportunity Scholarship of the Eidgenössische Technische Hochschule Zurich (to A. C. T), European Research Council Grant “Metabolomirs,” the Starr Foundation International, and the Swiss National Science Foundation National Center of Competence in Research on RNA Biology and Disease (to M. S.). M. S. is a member of the scientific advisory board of Regulus Therapeutics and Alnylam Pharmaceuticals.