Mobile MicroRNAs Direct Tissue Patterning

Scientists have been working for more than a decade to understand how tiny molecules called microRNA regulate genes within cells. Now researchers have discovered that microRNA actually moves between cells to help them communicate with each other and ultimately determine the types of cells that grow and develop.

This discovery has broad implications in a wide range of fields, including medical gene therapy and bioengineering of crop plants. The discovery could be especially useful in the production of biofuels, where being able to control the types of cells that develop could yield more useable plant matter.

The research – conducted at the Boyce Thompson Institute for Plant Research (BTI) in collaboration with Duke University and the Universities of Helsinki and Uppsala – was published online in the journal Nature on April 21.

The discovery of this molecular pathway represents the first time researchers have demonstrated that microRNA – small ribonucleic acid molecules that function to turn off genes in an organism – move between cells as a regulatory signal.

“Many organisms are made up of multiple types of cells, and we do not yet fully understand how these cells are put in the right places, although we believe cells communicate with each other ,” said Ji-Young Lee, assistant scientist at BTI and a lead author of the article. “This is the first time anyone has clearly demonstrated cells are communicating through the movement of microRNA. It’s likely that this kind of communication process is generally happening in many cell types in many organisms.”

The researchers conducted the study in the root of Arabidopsis, a small flowering plant related to cabbage, where they took a closer look at the development of two types of root cells – protoxylem and metaxylem. These are key cells responsible for the transport of water and mineral nutrients in most terrestrial plants. Their goal was to determine the molecular pathway that leads to the differentiation of these two cell types.

Using a combination of molecular and cellular techniques including high-resolution imaging, they discovered a complex sequence of events at the molecular level that creates the distinction between protoxylem and metaxylem cells.

The researchers discovered that a protein molecule called SHORTROOT moves from the vascular cylinder to the endodermis, an inner skin within the root. Once there, it activates another similar protein, SCARECROW. Together, these proteins trigger the creation of the molecule microRNA 165/6. These microRNAs seem to move out of the endodermis as signaling molecules.

MicroRNA 165/6 dissolves a corresponding molecule of messenger RNA, which carries the chemical blueprint for creating proteins. High dosage of these messenger RNA molecules lead cells to become metaxylem, whereas low dosage leads to protoxylem.

Since microRNA 165/6 moves out from its source cells and dissolves their target messenger RNAs, in areas where there are high levels of microRNA 165/6, nearby cells are more likely to become protoxylem. In areas where there are lower levels of microRNA 165/6,cells turn into metaxylem.

There is reason to think that these interactions were key in the evolutionary transition from water dependent mosses to plants that grow as tall as Giant Sequoias 450 million years ago. That’s because the layer of cells the researchers studied builds a waterproof tube through which plants can carry water from roots to branches, leaves and flowers.

Other lead authors of the article include Annelie Carlsbecker of Uppsala University, Yrjo Helariutta of Helsinki University and Philip N. Benfey of Duke University. BTI post doctoral associate Jose Sebastian and graduate student Jing Zhou also contributed to the paper.

You can find the full article online at http://www.nature.com/nature/journal/vaop/ncurrent/full/nature08977.html