While DNA is known as the primary blueprint for life, ribonucleic acid (RNA) plays a diverse role. Once seen as just a messenger for genetic code, we now know of many RNA types with specialized functions. Among these is microRNA (miRNA), a class of small, single-stranded RNA segments about 21 to 23 nucleotides long.
Unlike messenger RNA (mRNA), which carries instructions for building proteins, miRNAs are “non-coding” and are not translated into proteins. Instead, they act as regulators that fine-tune the activity of other genes, much like a traffic controller for genetic information.
The Role of MicroRNA in Gene Regulation
MicroRNA’s function involves messenger RNA (mRNA). An mRNA molecule is a transcript of a gene’s DNA, carrying instructions from the nucleus to the cell’s ribosomes, where proteins are made. This flow of information is highly regulated to maintain cellular health.
MicroRNAs regulate genes after instructions are transcribed to mRNA but before a protein is made, a process called post-transcriptional regulation. A mature miRNA is loaded into a protein complex called the RNA-induced silencing complex (RISC). The RISC complex then searches for mRNA molecules with a sequence complementary to the miRNA it carries. A “seed region” of about six to eight nucleotides on the miRNA is important for this recognition.
When the RISC complex finds a matching mRNA, the miRNA binds to it, typically in the 3′ untranslated region (3′ UTR), an area of the mRNA that doesn’t code for protein but is important for regulation. This binding triggers one of two outcomes. If the match is near-perfect, the RISC complex can slice the mRNA, marking it for destruction. More commonly in animals, an imperfect match prevents the ribosome from translating the mRNA into a protein and leads to its eventual breakdown. This process effectively “silences” the gene by turning down its expression.
MicroRNA’s Impact on Bodily Functions
The control of gene expression by microRNAs is part of many physiological processes, ensuring cells develop, function, and are removed correctly. This regulation allows complex biological events to occur in an orderly fashion, maintaining the body’s health.
A primary role of miRNA is in cellular differentiation, the process where a stem cell becomes specialized, like a neuron or muscle cell. For example, two muscle-specific miRNAs, miR-1 and miR-133, work in balance. MiR-1 promotes the differentiation of muscle cells, while miR-133 encourages the proliferation of their precursors. This action ensures muscle tissue develops and repairs itself correctly.
MiRNAs are also involved in apoptosis, or programmed cell death. Apoptosis is the body’s natural process for eliminating old, damaged, or infected cells without causing inflammation, which is important for tissue homeostasis. By regulating the genes that control this process, miRNAs help ensure a healthy balance between cell death and cell proliferation, which is necessary for the proper turnover of cells.
The Link Between MicroRNA and Disease
When microRNA function goes awry, it can contribute to human diseases. The dysregulation of miRNA, meaning there is too much or too little of a specific one, disrupts the balance of gene expression. This imbalance can lead to the start and progression of conditions from cancer to heart disease.
In cancer, some miRNAs function as tumor suppressors, helping to control cell growth and promote apoptosis in abnormal cells. If these miRNAs are down-regulated or lost, their target oncogenes (cancer-causing genes) can become overactive, leading to tumor formation. For instance, the let-7 family of miRNAs is often under-expressed in lung cancer, contributing to the disease’s progression.
Conversely, some miRNAs act as oncogenes, or “oncomiRs.” When over-expressed, they can suppress genes that normally halt the cell cycle or induce cell death, promoting cancer. The miR-17-92 cluster, for example, is often amplified in lymphomas and solid tumors. In cardiovascular disease, dysregulation of miRNAs like miR-92a can impair new blood vessel growth, hindering recovery after a heart attack.
MicroRNA in Diagnostics and Therapeutics
The link between microRNAs and disease has opened new avenues for diagnostics and therapeutics. Because miRNAs are stable molecules released into body fluids like blood and urine, they are potential biomarkers. This stability has led to research into their clinical applications.
In diagnostics, miRNA profiles can be used as non-invasive indicators of disease. Diseased tissues, like tumors, often shed specific miRNAs into the bloodstream at detectable levels. Measuring these circulating miRNAs may allow for earlier detection of diseases like cancer or cardiovascular disorders. For example, elevated blood levels of specific miRNAs are being investigated as biomarkers for diagnosing pancreatic and prostate cancers.
For therapeutics, scientists are developing strategies to correct miRNA imbalances. One approach uses synthetic “miRNA mimics” to restore the function of a beneficial miRNA that is down-regulated. Conversely, for diseases caused by an overabundant miRNA, “anti-miRNAs” or “antagomirs” can be used. These molecules bind to and block the problematic miRNA, preventing it from silencing its target genes and restoring normal function.