Cardiac development needs more than protein-coding genes

When the human genome was sequenced, biologists were surprised to find that very little of the genome - less than 3 per cent - corresponds to protein-coding genes. What, they wondered, was all the rest of that DNA doing?

It turns out that much of it codes for genetic snippets known as long non-coding RNAs, or lncRNAs. In recent years, scientists have found that these molecules often help to regulate which genes get turned on or off inside a cell. However, little is known about the specific roles of the thousands of lncRNAs discovered so far.

In a new study, MIT biologists have identified a critical role for a lncRNA they dubbed ''Braveheart.'' This lncRNA appears to stimulate stem cells to transform into heart cells during mouse embryonic stem cell (ESC) differentiation; the researchers suspect that lncRNAs may control this process in humans as well. If so, learning more about lncRNAs could offer a new approach to developing regenerative drugs for patients whose hearts have been damaged by cardiovascular disease or aging.

''It opens a new door to what we could do, and how we could use lncRNAs to induce specific cell types, that's been completely unexplored,'' says Carla Klattenhoff, a pos-tdoc in MIT's department of biology and one of the lead authors of a paper describing the findings in the Jan. 24 online edition of Cell.

MIT postdoc Johanna Scheuermann is also a lead author of the paper. Senior author is Laurie Boyer, the Irwin and Helen Sizer Career Development Associate Professor of Biology at MIT.

The researchers zeroed in on the Braveheart lncRNA because they had noticed that it is abundant both in ESCs and in differentiating heart cells. In the new study, they found that without normal levels of the Braveheart lncRNA, mouse ESCs did not develop any of the three major types of heart cells that comprise the cardiovascular system - cardiomyocytes (which make up cardiac muscle), smooth muscle cells and endothelial cells.