microRNA (miRNA), small molecule in cells, typically about 21–25 nucleotides in length, that plays a crucial role in the regulation of gene expression. MicroRNA (miRNA) is unique relative to other forms of RNA, which function primarily to carry and translate the genetic code from DNA into protein. By contrast, miRNA neither carries codes from DNA (and thus is described as “noncoding”) nor engages in the production of proteins; in fact, it regulates genes by silencing protein synthesis. The first miRNA was discovered in the early 1990s by American scientists Victor Ambros and Gary Ruvkun, who shared the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking research.
MicroRNAs originate from longer, double-stranded RNA precursors. These precursors are processed in the nucleus and cytoplasm to form mature, single-stranded miRNAs. Mature miRNAs regulate gene expression posttranscriptionally—that is, after RNA has been generated by the process of transcription and before it undergoes translation. Regulation is exerted when miRNAs attach to molecules of messenger RNA (mRNA), which transport DNA codes from the nucleus to protein-synthesizing ribosomes in the cytoplasm. This binding action prevents protein synthesis because it causes either mRNA degradation or translational repression, in which translation is inhibited without necessarily degrading the mRNA. In some instances, mRNA that has been tagged by miRNA binding is preserved for later translation.
Gene regulation by miRNA serves an essential role in fine-tuning the genetic control of fundamental processes, such as cell differentiation, cell growth, and cell death. In particular, miRNA helps cells to respond dynamically to environmental signals and exerts temporal control over specific genes, ensuring that they are expressed at the appropriate time and in the correct amounts. The latter is especially important during embryonic development, when miRNAs regulate the expression of genes that are responsible for guiding stem cells to mature into specialized cell types. For example, specific miRNAs direct the development of muscle cells, neurons, and immune cells by controlling the timing and level of gene expression necessary for each cell type.
Aberrant miRNA expression is associated with a wide range of diseases, including certain autoimmune diseases, cancer, cardiovascular disease, and neurodegenerative disorders. For example, certain microRNAs can function as oncogenes (which induce cancer) or as tumor suppressors (which inhibit cancer), depending on whether they upregulate or downregulate key genes involved in cell proliferation.