microRNA - What It Is and How It Works
microRNA is the name of a family of molecules that helps cells control the kinds and amounts of proteins they make. That is, cells use microRNA to help control gene expression. Molecules of microRNA are found in cells and in the bloodstream. (Note: microRNA is abbreviated “miRNA,” but here we will use “microRNA” throughout.)
Gene expression refers to whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.
To understand gene expression and how microRNA works, it’s helpful to know how cells use a gene’s DNA to make a protein. It happens through a four-step process called protein synthesis.
(If you are familiar with protein synthesis, skip ahead to “How microRNA controls gene expression.”)
The four-step process of protein synthesis
Step 1: Gene activation
- A cell begins making a protein by activating the gene that contains the information for the protein. A protein called a transcription factor binds with the gene, and this activates it.
Step 2 – gene transcription
- The DNA for the activated gene opens up, exposing the gene’s DNA sequence.
- The gene’s DNA sequence is copied in the form of RNA.
- This RNA copy of the gene is called messenger RNA, or mRNA.
Step 3 – editing of the mRNA
- Unneeded bits of the mRNA are cut out and removed.
- The remaining, mature, mRNA molecule then leaves the cell nucleus and enters the cell cytoplasm.
Step 4 – translation
- In the cytoplasm, small structures – molecular machines – called ribosomes attach to the mRNA
- The ribosomes begin at one end and move along the mRNA strand, “reading” the sequence of bases (i.e., the copy of the gene)
- As they do so, they attach amino acids one by one to make a growing chain that becomes the final protein
microRNA works by binding with a gene’s mRNA in the cytoplasm. This will prevent or delay its translation (step 4).
How microRNA controls gene expression
microRNA controls gene expression mainly by binding with messenger RNA (mRNA) in the cell cytoplasm. Instead of being translated quickly into a protein, the marked mRNA will be either destroyed and its components recycled, or it will be preserved and translated later.
So, if the level of a particular microRNA is underexpressed (its level in the cell is abnormally low), the protein it normally regulates may be overexpressed (its level will be unusually high in the cell); if the microRNA is overexpressed (its level is unusually high), its protein will be underexpressed (its level will be unusually low).
microRNA and cancer
Along with genes that encode the information for making proteins, cells have genes that encode the information for making microRNA.
- In cancer cells, microRNA genes can be damaged by mutations
- A mutation in a microRNA gene can leave the cell without that particular microRNA or reduce it a low level in the cell.
- Abnormally low levels of a microRNA can lead to overexpression of genes that that microRNA regulates, and that can lead to cancer development and progression. (Note: a particular microRNA can regulate hundreds or thousands of genes by binding with their mRNA.)
- Abnormal expression of microRNA has been implicated in many human cancers
The Birth and Life of a microRNA Molecule
Genes for microRNA are as much a part of the human genome as genes that code for proteins. Cells make microRNA using a process that resembles the early steps of protein synthesis. The microRNA gene is activated, the DNA strand opens up and the gene is copied, or transcribed, in the form of RNA.
- The initial gene transcript is called primary miRNA (pri-miRNA)
- In the cell nucleus, these hairpin-loop molecules are cut to form double-stranded precursor miRNA (pre-miRNA)
- The pre-miRNA is transported to the cytoplasm. There, it is further cut to form a functional mature miRNA (mature miRNA molecules are about 22 nucleotides long)
- The mature miRNA first binds with a molecule called the RNA interference silencing complex, or RISC
- Then the miRNA binds with its target messenger RNA (mRNA), thereby blocking its translation or prompting its degradation