Dr. Srivastava said that if the microRNA is not functioning properly, heart development could be affected in many ways, including not having enough cells or having too many cells in certain locations.
"There are a variety of things that are critical to any organ's development," he said. "The Hand2 protein is a master regulator, and in its absence, you don't get any expansion of the heart ventricle at all. The finding that this microRNA controls Hand2, and probably several other proteins, is very significant."
The UT Southwestern research team is currently screening human patients with congenital heart disease for mutations in the gene miR-1 to determine what health effects such a mutation might cause. They also are studying mice and fruit flies lacking miR-1.
Dr. Srivastava said the field of microRNA studies has only recently begun to blossom. One of the key challenges is to determine which messenger RNA any given microRNA will target. Hundreds of genes are known to produce microRNA, but in vertebrates there are only three or four known targets for those hundreds.
"We are learning that microRNAs are a common mechanism through which a cell regulates itself at various stages, both during development and later in life," he said. "This is a rapid way to regulate protein levels. You can imagine a pool of messenger RNA ready to make a protein, and by virtue of a microRNA, that protein synthesis can immediately be shut off and turned back on based on a cell's environment or its needs at the time."
Dr. Yong Zhao, a postdoctoral researcher in Dr. Srivastava's lab at UT Southwestern, developed a new method to predict targets for vertebrate microRNAs based on the genetic sequence of microRNA genes and the accessibility of the target mRNA. D
Source:UT Southwestern Medical Center