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Human Gene Expression Is Not Regulated by Bovine Milk Exosome MicrorRNAs in Normal HEK-293 Cells
Exosomes are nanoparticles (30-150 nm) produced by donor cells that are delimited by a double lipid bilayer and are unable to self-replicate. Exosomes transport internal cargo (e.g., nucleic acids, proteins, lipids, metabolites) between cells for intercellular communication. Exosomes are found in high concentrations in bovine milk and may be important for intercellular communication between a cow and her calf. miRNAs are a conserved class of single-stranded (19-24 nt long), noncoding RNA molecules that regulate gene expression by binding to miRNA Response Elements (MREs) in mRNAs as part of the RNA Induced Silencing Complex (RISC). miRNA binding decreases gene expression by destabilizing target mRNAs and/or inhibiting translation. If miRNAs in bovine milk exosomes (BMEs) are functional, the miRNA sequences and the corresponding MREs should be conserved and at least a subset of these miRNAs should be consistently present in BMEs. A comparative genetics approach was used to assess conservation of BME miRNAs and their MREs. BME miRNAs and their MREs are conserved across species, and most miRNAs are consistently present in BMEs. BME miRNAs are also under selective pressure to maintain their sequences suggesting that they have an important function. Further BMEs are absorbed across the basolateral membrane of intestinal cells into human blood after a milk meal. Because BME miRNAs are conserved, they have the potential to regulate human gene expression and therefore, affect risks associated with diseases/disorders from the long-term consumption of cow’s milk. HEK-293 cells, a well-established model system for the investigation of miRNA function, were treated with BMEs to examine exosome uptake and gene expression. BMEs are taken up by HEK-293 cells, with maximum miRNA levels at 48 hours posttreatment. No BME miRNA-mediated changes in gene expression were observed in normal HEK-293 cells, but changes were detected in infected HEK-293 cells. Understanding the molecular intricacies associated with the consumption of dietary exosome miRNAs is crucial for comprehending how dietary miRNAs may affect human disease risks by regulating gene expression.
Genetics|Cellular biology|Molecular biology
Meinders, Katie A, "Human Gene Expression Is Not Regulated by Bovine Milk Exosome MicrorRNAs in Normal HEK-293 Cells" (2023). ETD collection for University of Nebraska - Lincoln. AAI30420305.