June 18, 2004 -- (BRONX, NY) -- In a paper appearing in the June 18th issue of Science, researchers at the Albert Einstein College of Medicine of Yeshiva University have solved the mystery surrounding cell biology’s greatest escape: the crucially important migration of messenger RNA molecules out of the cell’s nucleus so that genetic instructions can be translated into proteins.
The discovery was made possible by cutting-edge microscope technologies, developed at Einstein, in the laboratory of Dr. Robert H. Singer, and allows scientists to view individual molecules and track their movement within the cell. This study represents the first time that single molecules have been visually monitored in the cell nucleus.
Directions for making proteins are encoded by the genes — the sequences of DNA molecules that reside on chromosomes in the nucleus of each cell. But for a gene to make a protein, its DNA code must first be copied, or transcribed, onto a molecule called messenger RNA. These RNA molecules must then migrate from the nucleus and into the cytoplasm, where the cell’s protein-making machinery resides.
For years, researchers have puzzled over how these RNA molecules travel through the nucleus until eventually exiting through tiny holes called nuclear pores. Speculation has centered on a possible role for actin and myosin (proteins involved in muscle movement) or for molecules of ATP (the energy source for most physiological reactions in cells) to help the molecules move out.
To answer the question, Einstein researchers rendered single molecules of messenger RNA visible by labeling them with multiple copies of yellow fluorescent protein. These “tagged” messenger RNA molecules could then be followed under the microscope as they moved around the nucleus and towards the cytoplasm.
“As we tracked these messenger RNA molecules that make gene expression possible, we found no evidence that their movement is directed in any way,” says Dr. Robert Singer, co-chairman of the Department of Anatomy and Structural Biology at Einstein and senior author of the study. “Instead, we reached the somewhat counterintuitive conclusion that that messenger RNA molecules move through the nucleus by simple diffusion, which turns out to be a very efficient process for their export.”
The other Einstein researchers were lead author Yaron Shav-Tal, Xavier Darzacq, Shailesh M. Shenoy and Dahlene Fusco. Susan M. Janicki and David L. Spector of Cold Spring Harbor Laboratory also collaborated on the study.