microRNA
/ MY-kro-AR-en-ay /
Imagine a busy kitchen full of recipe slips (the mRNAs), each waiting to be cooked into a dish (a protein). Now imagine a small inspector who can quietly stamp certain slips with hold — cook this one less, or not at all. MicroRNAs are those inspectors: tiny RNA molecules that don't code for any protein themselves but tune down how much protein other genes make.
A microRNA is very short — only about 22 nucleotides. It works by base-pairing: part of its sequence matches a stretch in a target mRNA, usually in that mRNA's 3' untranslated tail region. Carried by a protein partner (Argonaute) inside a complex, the microRNA guides that complex to any mRNA whose sequence it matches, and the complex then either blocks the message from being translated or marks it for shortening of its poly-A tail and decay. Because the match needs only a short seed of about six to eight bases, one microRNA can dampen dozens or hundreds of different mRNAs, and one mRNA can be targeted by several microRNAs.
MicroRNAs turn out to be a pervasive layer of gene regulation. Animals and plants have hundreds of them, and they collectively fine-tune a large fraction of all genes — shaping development, keeping cell types stable, and responding to stress. Their discovery, starting in tiny roundworms in the 1990s, was another blow to the idea that non-coding RNA is junk: here was a whole class of functional RNAs hiding in the supposed noise, important enough that their misregulation features in cancers and other diseases.
The first known microRNA, lin-4 in the roundworm C. elegans, base-pairs with the mRNA of a gene called lin-14 and holds its protein down at the right moment, controlling the timing of the worm's development. No lin-4 protein exists — the RNA itself is the regulator.
A 22-base RNA that codes for no protein can throttle dozens of genes by base-pairing with their mRNAs.
MicroRNAs usually dampen rather than fully silence — they nudge protein levels down by degrees, acting as fine-tuners and buffers rather than on-off switches. This is a real difference from the strong, near-complete silencing typical of small interfering RNAs.