Defining the Function of MicroRNAs

Cellular microRNAs have been thought to mainly exist in the cytoplasm. However, scientists at the University of Eastern Finland and the University of Oxford have shown that these small, naturally occurring RNA molecules are also abundant in cell nuclei. The study findings, published today in Scientific Reports, strongly suggest that microRNAs play a role in the expression of genes in the cell nucleus—an observation that is crucial for the development of novel gene therapy, among other things.

To get their results, the scientists first profiled the division of microRNAs in different parts of endothelial cells and discovered that a large share of microRNAs are enriched in cell nuclei. When the scientists exposed the cell culture to hypoxia, they noticed that changes in the concentrations of individual microRNAs mostly took place either in cytoplasm or in the cell nucleus.

The study suggests that microRNAs play a more central role in regulating the expression of genes in cells than previously thought. For instance, the scientists found that microRNA-210, a molecule previously strongly associated with hypoxia, is, in fact, especially abundant in the cell nucleus. This observation sheds light on previously unknown mechanisms that cells use to adapt to hypoxia.

MicroRNAs weaken the expression of their target genes by binding to the ends of their messenger RNAs in cytoplasm. The research team already showed ten years ago that synthetic microRNA molecules can regulate genes of therapeutic importance in animal models by targeting their impact on genes’ regulatory areas in cell nuclei. This discovery, along with subsequent research, led the scientists to assume that structurally similar microRNAs occurring naturally in cells also play a role in the regulation of genes in the cell nucleus.

“It is highly significant that these microRNAs targeting the cell nucleus can also increase the expression of genes, which is opposite to what happens in RNA interference,” says senior author Mikko Turunen. “This is a very important finding in view of novel gene therapy, for example.”