MicroRNAs in the CSF

MicroRNAs (miRNAs) constitute a potent layer of gene regulation that has only been recognized since the early 2000s. MiRNA genes are encoded in the genomes of all higher eukaryotes and transcription of these genes gives rise to miRNA precursor molecules (figure). Such precursors are processed to 20–24 nucleotide single-stranded mature miRNAs, which are subsequently incorporated into the RNA-protein complex known as the RNA-induced silencing complex (RISC). Within RISC, the miRNA functions as guide and directs RISC to target sites located on mRNAs, which very often are only partially complementary to the miRNA. The physical association with RISC leads to a reduced protein production from the target mRNA (figure). About 1,000 human miRNAs have been identified so far. Since miRNAs are only partially complementary to target sites, potential targets for any given miRNA can be predicted for many different mRNAs. It is thereby hypothesized that miRNAs regulate the expression of almost half of all human genes.¹ Consequently, dysregulation of miRNAs has been linked to inflammatory, degenerative, and neoplastic neurologic diseases. Furthermore, miRNAs can leave their intracellular environment where they normally function, and enter the bloodstream and other body fluids. The function of such circulating miRNAs remains largely elusive, but recent evidence indicates a possible role of miRNAs in cell-to-cell communication.²