Evidence of cross kingdom Regulation: Plant miRNA can regulate Human Low Density Lipoprotein receptor adaptor protein 1 (LDLRAP1)

For the past two decades, Lin Zhang, Dongxia Hou, Xi Chen and Donghai Li have been working in existence of plant miRNA in human serum, calf serum and other mammals serum. Here is the first report that "plant miRNA can regulates the human LDLRAP1".

http://immunotrends.blogspot.com/2010/05/micrornas-mirna-are-small-noncoding_8794.html

MicroRNAs (miRNAs), a class of 19-24 nucleotide long non-coding RNAs derived from hairpin precursors, mediate the post-transcriptional silencing of an estimated 30% of protein-coding genes in mammals by pairing with complementary sites in the 3′ untranslated regions (UTRs) of target genes. miRNAs have been widely shown to modulate various critical biological processes,
including differentiation, apoptosis, proliferation, the immune response, and the maintenance of cell and tissue identity. We next characterized the possible carrier of circulating miRNAs. Microvesicles (MVs) are small vesicles that are shed from almost all cell types under both normal and pathological conditions [13, 14]. They bear surface receptors/ligands of the original cells and have the
potential to selectively interact with specific target cells and mediate intercellular communication by transporting Plant MIR168a downregulates mammalian LDLRAP1 bioactive lipids, mRNA, or proteins between cells.

Their previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

In this sense, miRNAs may represent a novel class of universal modulators that play an important role in mediating animal-plant interactions at the molecular level. Like vitamins, minerals and other essential nutrients derived from food sources, plant miRNAs may serve as a novel functional component of food and make a critical contribution to maintaining and shaping animal body structure and function. Extending from this concept, the intake of certain plant miRNAs generation after generation through a particular food source may leave an imprint on the genetic map of the human race. In conclusion, the discovery of plant miRNAs and their roles in the biology of mammalian cells and animal organs represents the first evidence of crosskingdom transfer of functionally active miRNAs and opens a new avenue to explore miRNA-mediated animalplant interactions.

Cell Research advance online publication 20 September 2011; doi:10.1038/cr.2011.158

http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2011158a.html