Energizing miRNA research: A review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways

Abstract

MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: 1. Adipocyte biochemistry and cell fate determination; 2. Regulation of metabolic biochemistry in invertebrates; and 3. Regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon a particular 'target' mRNA. Whereas in some biological contexts the effects of a given miRNA:mRNA pair may predominate, this might not be the case generally. In order to provide an example of how a single miRNA could regulate multiple 'target' mRNAs or even entire human metabolic pathways, we include a discussion of metabolic pathways that are predicted to be regulated by the miRNA paralogs, miR-103 and miR-107. These miRNAs, which exist in vertebrate genomes within introns of the pantothenate kinase (PANK) genes, are predicted by bioinformatics to affect multiple mRNA targets in pathways that involve cellular Acetyl-CoA and lipid levels. Significantly, PANK enzymes also affect these pathways, so the miRNA and 'host' gene may act synergistically. These predictions require experimental verification. In conclusion, a review of the literature on miRNA regulation of metabolism leads us believe that the future will provide researchers with many additional energizing revelations.

The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1

“…Intriguingly, miR-107 expression may relate to the coordinated regulation of a pathway related to lipid metabolism (Wilfred et al, 2007). The DNA templates for miR-107 and miR-103 each exist within introns in the genes that encode the pantothenate kinase (PANK) enzymes.…”

“…miR-103(1), miR-103(2), and miR-107 reside within PANK3, PANK2, and PANK1 genes, respectively (Ying and Lin, 2005). The basic arrangement of these miRNAs in PANK genes remains constant through 500 million years of vertebrate evolution (Wilfred et al, 2007). PANK enzymes serve a universal catalytic function, namely, the phosphorylation of pantothenate (vitamin B5) (Tahiliani and Beinlich, 1991).…”

Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

“…In one case, miR-103 and miR-107 were found to be encoded within an intron of the PANK gene in a pattern that is conserved among a large array of organisms [148]. Both microRNAs (the high degree of sequence homology makes them virtually indistinguishable) are predicted to target a large number of genes involved in acetyl-CoA and lipid metabolism.…”

Tiny Actors, Great Roles: microRNAs in p53's Service

“…6 A current challenge in the field is to determine the functions of the various microRNAs in normal physiological processes as well as in disease. miRNAs have already been impli- Nina raver-shapira moshe Oren* p53 and microRNAs cated in the control of many fundamental biological processes such as development and immunity, 7-9 cell differentiation and proliferation, 10 metabolic and signaling pathways, [11][12][13] apoptosis and stem cell maintenance. 14,15 Of note, Dicer-deficient mouse and zebrafish embryos are stalled at an early developmental stage, leading to developmental arrest, small size, morphological abnormalities and lethality.…”