RNA splicing is topic for Nobel Laureate Sharp’s lecture

Phillip A. Sharp

Scientists work around the clock trying to understand precisely how RNA segments are spliced in the subregions of our cells. All our hereditary data, including genetic disease, is passed on at this level. What chemical reactions take place? Can the process be regulated? How is the RNA itself formed?

In light of recent cloning and gene therapy advances, it may be surprising to hear investigators say that little is known about this process. The fact is that what knowledge there is has come rapidly and dramatically. In the early 1970s, biotechnology companies did not exist. Genetic research was conducted primarily in academic labs. The first biotech company, Genentech Inc., was founded in 1976. Today, there are hundreds of biotech companies around the world.

One of the key events that triggered this explosion in molecular biology was the discovery of the “split gene” in 1977 by Dr. Phillip A. Sharp, at the time an associate professor in the Center for Cancer Research at Massachusetts Institute of Technology. Sharp, now the Salvador E. Luria Professor of Biology and head of the Department of Biology at MIT, and Dr. Richard J. Roberts, who made the discovery separately at Cold Spring Harbor Laboratory on Long Island, New York, received the 1993 Nobel Prize in Physiology or Medicine for their work.

Sharp will be at the UW to present the School of Medicine’s Annual Science in Medicine Lecture on Friday, March 26, from 3 to 4 p.m. in room T-625 of the Health Sciences Center. His lecture is titled “The Biology of RNA Splicing.”

For most of us, adenovirus is a pesky, resistant virus that causes the common cold. Rapid gene expression and a simple genomic structure — all its genes are present in a single DNA molecule — make the adenovirus a revealing organism for researchers to examine.

Working independently, Sharp and Roberts were attempting to identify the location of genes on the DNA molecule in the adenovirus nucleus. Using electron microscopy, they found that single RNA segments corresponded to separate segments of DNA in the larger molecule. In other words, they found that genes exist as discontinuous segments on a DNA molecule.

Previously, scientists believed that genes existed as single segments on DNA molecules and were copied to single RNA molecules when activated. From RNA segments, our genetic data is transcribed into proteins, the building blocks of all bone, tissue and muscle in our bodies.

The discovery of the split gene, which scientists now know is the most common gene structure in higher organisms, including humans, has led to many other discoveries. It is now known that genetic function is determined by how RNA segments are spliced together and that the same RNA segments are combined differently to produce different proteins. Sharp’s work is now primarily focused on identifying the chemical agents responsible for activating and regulating this RNA splicing.

In 1978, a year after the split gene discovery, Sharp and several colleagues founded a company called Biogen, which is today among the world’s largest biotechnology companies. Sharp is currently chair of Biogen’s scientific board and a member of its board of directors.

Between 1985 and 1991, Sharp directed MIT’s Center for Cancer Research. He has been a professor of biology at MIT since 1979. His honors and awards include the General Motors Research Foundation Alfred P. Sloan, Jr. Prize for Cancer Research, the Louisa Gross Horwitz Prize from Columbia University, and the Albert Lasker Basic Medical Research Award. ¶

Will Morton