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Gene control hits new level

January 17, 2005 By Helen Pearson This article courtesy of Nature News.

Tiny RNA molecules prove more influential than imagined.

More than one-third of human genes could be controlled by minuscule molecules called microRNAs. This claim by US scientists suggests that the molecules, which were first discovered in 2000, could play a role in almost every process from cell birth to cell death, and that they might even be useful in treating human disease.

MicroRNAs are rather like fragments of DNA, and are made up of around 22 chemical 'letters'. They act as controls by effectively blocking a gene from doing its normal job in a cell.

When a gene is switched on, its sequence is converted into messenger RNA, which carries the information to make a protein. MicroRNAs recognize and bind to particular messenger RNAs and stop them from making proteins.

Scientists know that human cells are swimming in microRNAs, but have been unsure how many of our 22,000 or so human genes they control. They might affect only a few hundred genes, say some, or as many as several thousand.

Top scour

To reach their new estimate, David Bartel at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and his colleagues built a computer algorithm that scours messenger RNAs from human genes for characteristic genetic sequences, ones that show they are likely targets of microRNAs.

They checked whether these same sequences are present in the corresponding genes of the mouse, rat, dog and chicken. The idea that a gene is controlled by microRNAs in humans would be supported if the same gene seemed to be controlled by microRNAs in other animals.

At least one-third of our genes may be controlled by microRNAs, the team report in Cell1. This is a jump above previous estimates, such as one from last year that put the figure at 10% of genes or more2.

And because the new estimate is only a rough one, the true figure could be much higher, says team member Chris Burge of the Massachusetts Institute of Technology, also in Cambridge. For example, the study does not identify genes regulated by microRNAs in humans but not other animals.

Small but mighty

Indeed, microRNAs could control the action of almost every human gene, says Debora Marks who studies the molecules at Harvard Medical School in Boston, Massachusetts. This could make the process just as important as other major mechanisms for controlling gene action, such as those that use proteins to control whether a gene is switched on (to make messenger RNA) in the first place.

The discovery also supports the idea that when microRNAs go awry they may trigger anomalies such as the uncontrollable cell division that is typical of cancer.

Biotechnology companies are scrambling to work out how to use microRNAs to treat human disease. It is possible, for example, that a particular microRNA that blocks cancer could be given directly to a patient. Researchers already do something very similar when they silence genes with a technique called RNA interference or RNAi.

But although biologists are increasingly confident that microRNAs are fundamentally important, they are only just starting to figure out the details, such as how many of them there are. There are currently thought to be at least 250 or so different microRNAs, but another new study in Cell suggests that there could be 200-300 more3.

Next, scientists must work out exactly which genes are damped by each type of microRNA. "We're right on the cusp of knowing a lot more," says Marks. "It'll have a profound effect on all areas of biology and medicine."

References

  1. Lewis, B., Burge, C. & Bartel, D. P. Cell 120, 15–20 doi:10.1016/j.cell.2004.12.035 (2005).
  2. John, B. et al. PLoS 2, 1862–1879 doi:10.1371/journal.pbio.0020363 (2003).
  3. Berezikov, E. et al. Cell 120, 21–24 doi:10.1016/j.cell.2004.12.031 (2005).

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