B. Berkhout, R.H. Silverman, K.-T. Jeang, "Tat trans-activates the human immunodeficiency virus through a nascent RNA target," Cell, 59, 273-82, 20 October 1989.
Ben Berkhout (National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Md.): "The unique feature of this study was the use of RNA-refolding mutagenesis. Rearrangement of RNA structures was first described by Charles Yanofsky [Stanford University] to explain the process of transcriptional attenuation ["Transcription attenuation," Journal of Biological Chemistry, 263, 609-12, 1988]. In our study on the HIV-1 TAR [trans-acting responsive] element, we forced this RNA hairpin motif into an alternative structure by inserting stretches of complementary nucleotides adjacent to TAR. Such mutant TAR elements, although unchanged in actual sequence, did not respond to the HIV-1 trans-activator protein Tat. We thus showed that correct folding of the TAR sequences is essential for function.
"Even more exciting was the behavior of `kinetic mutants' that only transiently adopt the...
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