Highly specific RNA enzymes synthesized The molecular components responsible for the catalytic activity inherent in some naturally occurring ribonucleic acids have been determined and subsequently incorporated into synthetic RNA enzymes that catalyze with high specificity the cleavage of target RNA molecules [Nature, 334,585 (1988)]. The synthetic enzymes were produced by Jim Haseloff and Wayne L. Gerlach, scientists with Australia's Commonwealth Scientific & Industrial Research Organization in Canberra. Haseloff and Gerlach call the RNA enzymes " r i b o z y m e s " and suggest that they could find application in the manipulation of RNA molecules, either to produce large amounts of particular RNA fragments or as a means of physically mapping RNAs. The researchers point out that another potential application of ribozymes is the in-vivo cleavage and inactivation of target messenger RNA molecules. DNA that encodes a ribozyme targeted against a particular mRNA transcript could be introduced into the genome of a bacterium, plant, or animal using established techniques. The ribozyme then produced by the genetically e n g i n e e r e d cell would catalyze the cleavage of only the target mRNA, in effect inhibiting the expression of the corresponding gene. Such a strategy might find use as a therapy against genetic diseases and viral infections. According to Haseloff, a number of experiments are under way to tesi the feasibility of this application. Haseloff and Gerlach studied the RNA genome of tobacco ringspot virus (sTobRV), which is known to act as an enzyme in its own cleavage. The scientists isolated three domains in the RNA necessary for the catalytic cleavage reaction to occur: a three-nucleotide signal sequence (guanine-uracil-cytosine or GUC) that lies adjacent to the cleavage site; a region of highly conserved sequence and secondary structure that appears to act as the catalytically active site; and flanking regions of base-paired RNA helix that stabi-
lize the interaction of the first and second domains. The GUC signal sequence can be found scattered throughout RNA molecules. Haseloff and Gerlach constructed ribozymes that would cleave chloramphenicol acetyl transferase (CAT) mRNA by choosing three GUC cleavage signal sites in the CAT mRNA. They attached the catalytic domain of sTobRV to RNA sequences capable of base-pairing with the regions in the CAT mRNA
flanking these three GUC signal sites. Each resulting ribozyme cut CAT mRNA in only one position. To establish that the reactions were truly catalytic, the researchers incubated each ribozyme with an excess of substrate under conditions that favored cleavage and product dissociation. On average, each ribozyme molecule participated in more than 10 cleavage events, the researchers report. Rudy Baum
More safety planning urged for DOE reactors A new report from the National Research Council contends that the research reactors operated by the Department of Energy are in need of better safety planning. The five reactors studied vary in size and purpose, but NRC recommendations for items such as safer working conditions for reactor operators and proper risk assessments apply to all of them. The report was a consequence of the April 1986 accident that destroyed part of the Chernobyl nuclear power plant in the U.S.S.R. Officials concerned about the safety of U.S. reactors requested NRC to review safety and technical issues at the nation's so-called Class A reactors, those capable of producing more than 20 MW of thermal power. "NRC has presented DOE with a very constructive analysis of the issues relating to reactor safety, and I welcome their recommendations/' says DOE Secretary John S.
Herrington. "The department has made structural, long-term changes in response to previous NRC recommendations, and we will continue to do so." The report is divided into two parts. The first describes generic safety issues, and the second goes into detail about technical issues at each of the five reactors. The reactors are the Advanced Test Reactor and the Experimental Breeder Reactor II at the Idaho National Engineering Laboratory; the Fast Flux Test Facility at the Hanford Nuclear Reservation, Richland, Wash.; the High Flux Isotope Reactor at Oak Ridge, Tenn.; and the High Flux Beam Reactor at Brookhaven National Lab on Long Island. The select panel chosen for the review, chaired by Richard A. Meserve of the Washington, D.C., law firm Covington & Burling, observes that "the real challenge confronting
Fast Flux Test Facility, Richland, Wash., used in research on nuclear fuels and materials, was one of five reactors studied by National Research Council panel August 22, 1988 C&EN
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