Genetic information flows from DNA to RNA to protein, a fundamental process. Messenger RNA (mRNA) acts as an intermediary, carrying the genetic instructions from the DNA within the cell’s nucleus to the ribosomes, where proteins are manufactured. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a significant role in regulating gene expression. These tiny molecules influence how much protein is made from an mRNA molecule. While miRNAs can indeed lead to the degradation of mRNA, they also regulate gene expression through other mechanisms.
The Key Players: mRNA and miRNA
Messenger RNA (mRNA) carries instructions for building specific proteins from DNA to the cytoplasm. Ribosomes read mRNA, like a recipe card, to assemble proteins. This molecule is single-stranded and its sequence directly dictates the order of amino acids in a protein.
MicroRNAs (miRNAs) are small, single-stranded RNA molecules. MiRNAs are non-coding, meaning they do not carry instructions for making proteins. Instead, they act as regulators of gene expression, functioning like a dimmer switch that controls the amount of protein produced from an mRNA molecule.
How miRNA Regulates mRNA
MiRNAs function as part of a larger cellular machinery. These small RNA molecules associate with a group of proteins to form what is known as the RNA-induced silencing complex (RISC). The miRNA within the RISC acts as a guide, directing the complex to specific messenger RNA (mRNA) molecules.
The guidance of the RISC complex to its target mRNA is based on sequence complementarity. The miRNA “matches” a particular sequence, primarily located in the 3′ untranslated region (3’UTR) of the target mRNA. This match is often imperfect in animals, which allows a single miRNA to regulate multiple different mRNA transcripts. A specific region of the miRNA, known as the “seed region,” is particularly important for this target recognition.
The Outcomes of miRNA Action
Once the RISC-miRNA complex binds to a target mRNA, it can influence the mRNA’s fate in one of two primary ways. If the miRNA has a near-perfect sequence match to its target mRNA, the RISC complex can cleave the mRNA molecule. This action, often carried out by the Argonaute protein within RISC, leads to the rapid degradation of the mRNA, effectively eliminating the genetic “recipe.”
More commonly, particularly when the miRNA has an imperfect match to its target mRNA, the RISC complex does not cut the mRNA. Instead, it represses, or blocks, the translation of the mRNA into protein. This means the mRNA molecule remains present in the cell, but the ribosomes are unable to read it and synthesize the corresponding protein, acting like a “pause button” or “stop sign” for protein production. Translational repression can occur through various mechanisms, including inhibiting the initiation of protein synthesis, or leading to the shortening of the mRNA’s poly(A) tail (deadenylation) and subsequent removal of its 5′ cap (decapping), which destabilizes the mRNA over time. The specific outcome, whether it is mRNA degradation or translational repression, depends on factors such as the degree of complementarity between the miRNA and the mRNA, and the specific proteins that are part of the RISC complex.
Why This Matters: The Biological Role
The ability of microRNAs to regulate gene expression is fundamental to nearly every aspect of cellular function and organismal development. They fine-tune the production of proteins, ensuring that genes are expressed at the appropriate time and in the correct amounts. This precise control is essential for processes like cell differentiation, where cells specialize into different types, and cell growth, which governs the increase in cell size and number.
MiRNAs also play a role in programmed cell death, known as apoptosis, which is a necessary process for removing damaged or unwanted cells to maintain tissue health. Furthermore, they are involved in the immune response, helping the body defend against pathogens, and in stress responses, enabling cells to adapt to changes in their environment. When miRNA regulation goes awry, it can contribute to various diseases, including different types of cancer and neurological disorders, highlighting their importance in health and disease.