Barbara Golden, 492-8304
Jennifer Doudna, (203) 432-3108
Jim Scott, 492-3114
Sept. 19, 1996
Note to Editors: Contents embargoed for use until 4 p.m. EDT Thursday, Sept. 19.
KEY MOLECULAR PLAYER IN ORIGIN OF LIFE SEEN IN ATOMIC DETAIL FOR FIRST TIME
A team of U.S. researchers has cracked the three-dimensional atomic structure of a large molecule of the genetic material RNA, a feat that has implications both for the origins of life and for future biomedical research.
Imaging of the ribonucleic acid, or RNA, molecule was achieved after four years of research by scientists from the University of Colorado, the Howard Hughes Medical Institute and Yale University. The scientists grew crystals of a key region of a large RNA enzyme, or ribozyme, then used x-ray beams to analyze the positions of atoms and accurately reconstruct the shape of the molecule.
The Colorado research team was led by Thomas Cech, a chemistry and biochemistry professor at CU-Boulder and a Howard Hughes Medical Institute Investigator. Other members of the Colorado research team include HHMI researchers Anne Gooding, Elaine Podell and Barbara Golden and CU-Boulder Professor Craig Kundrot.
The Yale research team was led by Professor Jennifer Doudna and included researchers Jamie Cate and Kaihong Zhou.
The new image proves that RNA enzymes are densely packed and highly organized, said Cech. The image shows how the double-helix-shaped regions of the molecule are packed together with the aid of "glue" provided by magnesium ions commonly found in living organisms today. Because these ions are abundant in the oceans, they presumably were available long before life evolved on Earth.
"The new, three-dimensional images show the level of organization of RNA that allows it to act as an efficient biological catalyst or RNA enzyme," said Cech. "Such molecules may have reproduced themselves in a primordial RNA world."
Results of the project were published in two papers in the Sept. 20 issue of Science, the nation's leading weekly science journal.
Cech shared the 1989 Nobel Prize in chemistry with Yale Professor Sidney Altman for their independent discoveries that RNA, like proteins, can act as catalysts in living cells. The finding prompted widespread belief among scientists that RNA likely played a key role in the origin of life.
The research project ends a 23-year drought in imaging of large RNA structures. In 1973, the crystal structure of a type of RNA known as transfer RNA was solved by a team led by Sung-hou Kim, now at the University of California at Berkeley, and Alexander Rich of the Massachusetts Institute of Technology. Containing more than 9,000 atoms, the piece of RNA enzyme imaged by the Colorado-Yale researchers is more than twice as large as the transfer RNA structure, said Cech.
Key funding for the Colorado portion of the effort was made by the W.M. Keck Foundation of Los Angeles, said Cech.
The research indicates the compact and efficient architecture of RNA enzymes is achieved in part as a result of several recurring chemical patterns that form "platforms" built from different combinations of four nucleotides. Such recurring platforms facilitate the folded shape of the molecule.
The new RNA image may help scientists answer the often cited "chicken-and-egg" question concerning the origin of life -- whether the informational molecule (nucleic acid) or the functional catalyst (protein enzyme) came first. The new three-dimensional structure provides further evidence that RNA has very sophisticated catalytic potential, he said.
The groundbreaking RNA crystallography work also may spur efforts to crystallize particular regions of viral RNAs, he said. Viruses including HIV-1, polio, the common cold and flu all use RNA as their genetic material.
In addition, ribozymes are being developed as gene therapy agents to repair defective cellular RNA that causes genetic diseases like sickle cell anemia, muscular dystrophy and cystic fibrosis. "Having the detailed structural information provided by the new images may spur efforts to design new molecular repair kits for defective RNA," Cech said.
For now, said Cech, scientists are "simply stunned by the beauty of the RNA molecule" and excited to learn more about the molecular architecture that allows simple chemical building blocks of RNA to organize themselves so specifically.
Cech also is a faculty member at the CU Health Sciences Center in Denver.