Freshly Baked Science
microRNAs: Going Underground to Find The Perfect Match
1st June 2019
All cells in our body have the same genetic information, so why is a brain cell so different from a skin cell? This can be explained by genes being turned on or off at different points in time. An RNA is a midway molecule, made from a DNA sequence, that can be read to make a protein. microRNAs are short RNAs that don’t make proteins but are thought to affect which genes are turned on by potentially silencing them.
An area of key importance for these short strings is disease. microRNAs are currently being implicated in many different types of cancer. This is important as they could be controlling when certain genes are expressed and triggering the development of certain tumours. It will be interesting, in the coming years, to see the research develop and give us more insight on how the little strings have a big impact, and how they could be targets for future therapies. But for now, let’s take a journey underground and look at how microRNAs can affect gene expression.
First stop: how do cells know when and where to produce these building blocks? You wouldn’t be surprised to know that the processes for making proteins in the body are finely regulated by strict instructions. Different signals fire around inside cells and can create an environment that makes the cell know it needs to produce more or less of something e.g. a fat cell needs to make more fat. This is much like following the tube map, get on the wrong line and you’ll end up in the wrong place… mind the gap!
Each building block in our body starts off as a piece of DNA; a double-stranded winding string of adenine, thymine, guanine and cytosine residues (A’s, T’s, C’s and G’s). This gets unzipped by a naughty enzyme, called DNA helicase, unwinding the tangled DNA. This is then further unwound by another enzyme, topoisomerase, and the individual strands of DNA are kept separated by proteins. Transcription is where a copy of the DNA is made into an mRNA (messenger RNA) molecule by RNA polymerase. Next, the mRNA sequence is read by something called a ribosome, as this is being done, tRNAs will bring amino acids that correspond to the mRNA sequence being read. The sequence is read in three letters at a time in a process called translation, where the three letters code for an amino acid, of which there are 21 varieties. The amino acids are put together like a string and form a polypeptide. This polypeptide then folds and bends to make a protein before going off to its final stop.
Gene expression pathways can be complicated and scientists often like to map out patterns. The London underground has 11 different tube lines, covering 270 stations. Currently, there are 1,872 known microRNA genes in humans, which can produce over 2,500 different microRNAs; that’s a big map! microRNAs are short interfering strings of information that can block the production of those building blocks and can, therefore, affect gene expression. microRNAs are produced in the cell nucleus and are pushed out into the cell body by proteins called exportins. In the cytoplasm, the microRNA is free floating. Think of the microRNA as a sticky molecule looking for its complementary friend, a matching mRNA sequence. Like two single souls looking for their perfect match in London. The microRNA will bind to the seed region of a gene, the matching mRNA sequence. This is how the effect of the microRNA is targeted to a specific gene.
OK, so where do microRNAs impact this journey? Let’s think of this whole process of an mRNA to protein as a long journey, like a trip on the London Underground. The trip to get to become protein X starts on the central line at Liverpool Street and reaches its final destination at Epping. The underground can seem quite complicated at first and so it is easy to go in the wrong direction or get off at the wrong stop. If you’re lucky you’ll have some help from a map or one of the happy staff at the underground. Like a regulatory protein, they will put you back on the right track.
But say you get off at the wrong stop, and maybe got distracted, say it’s a cold day, so you stop for a coffee in Starbucks or Greggs. While you’re there you might bump into a whole host of signals, bamboozling molecules or even a microRNA. Before you know it, you’re stuck together with the microRNA; matching perfectly, shared interests and shared seed regions. The microRNA of your dreams found you and you got distracted on your original journey and have embarked on a whole new one. Once bound, this pair of new-found lovers can instigate a whole host of effects, but as can happen with a bad Tinder match, things might not work out and the gene may never be expressed at all. This illustrates how a microRNA can find a complementary partner and affect how our genes are expressed.
Inui, M., Martello, G., and Piccolo, S. (2010). MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11, 252-263.
Peng, Y., and Croce, C.M. (2016). The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1, 15004.
microRNA- a short piece of non-coding RNA. An RNA that doesn’t make a protein but instead, can interfere with gene expression
DNA helicase- an enzyme that unwinds DNA, separating the double stranded DNA helix stands ready for copying.
Topoisomerase- These enzymes can cut DNA strands to help further untangle them.
Transcription- Copying of the DNA sequence and making an RNA molecule, this is done by enzymes called RNA polymerases.
RNA/mRNA- Ribonucleic acid, a molecule used in gene expression, producing the information needed to generate a sequence of messenger RNA (mRNA) to be read by ribosomes.
Transfer ribonucleic acid (tRNA)- an RNA molecule that decodes mRNA. The tRNA carries amino acids to generate polypeptides.
Translation- the process where ribosomes synthesize proteins in the cell cytoplasm.