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RNA lariat may tie up loose ends to decades-old mystery of retrovirus life cycle

ARLINGTON, Va.-Studies on common baker's yeast have led to the discovery of what may be a long-sought mechanism in the life cycle of retroviruses, including the human immunodeficiency virus (HIV). Knowing the details of this step in the infection process could help pinpoint targets for new classes of drugs to fight HIV.

In the Jan. 9 issue of the journal Science, Thomas Menees and Zhi Cheng of the University of Missouri-Kansas City describe the formation of a lariat structure with the genetic material of retrovirus-like elements in baker's yeast and subsequent cutting of the lariat by a yeast enzyme. The findings reported in Science and in the December 2003 Journal of Virology are the payoff of a three-year research gamble by Menees and two postdoctoral researchers pursuing host-cell factors in retroviral infections.

In addition to filling a gap in biologists' understanding of how retroviruses replicate, it may turn out that similar lariat structures occur elsewhere in healthy cells and play previously unrecognized roles in cellular processes such as gene activation.

"The work of Menees and his collaborators fills a real void in our understanding of how retroviruses propagate and how genetic information is faithfully copied," said Patrick Dennis, program director for microbial genetics at the National Science Foundation (NSF), which supported the research. "The RNA lariat provides a plausible mechanism for a key step that has remained a mystery since the process of reverse transcription was first presented almost 35 years ago."

The 1975 Nobel Prize in Physiology or Medicine was awarded to David Baltimore and Howard Temin, in part, for describing how retroviruses replicate. The genomes of most organisms are encoded in DNA, which is transcribed into single- stranded ribonucleic acid (RNA) and then translated into proteins. The genome of a retrovirus, on the other hand, starts as RNA, which must first be convert
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Contact: David Hart
dhart@nsf.gov
703-292-7737
National Science Foundation
8-Jan-2004


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