Reshuffling the Deck Evenly

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Science  23 Jun 2000:
Vol. 288, Issue 5474, pp. 2097
DOI: 10.1126/science.288.5474.2097c

Reverse transcriptase decodes the genetic information carried by the RNA genome of retroviruses. The viral nucleocapsid protein (NCp7 for HIV-1) is known to function as an RNA chaperone, enhancing the ability of the RNA genome to fold into a stable conformation and promoting annealing of complementary RNAs. Negroni and Buc now suggest that it also promotes genetic reshuffling in the retroviral world.

Because retroviral particles contain two single-stranded molecules of RNA, one mechanism for generating diversity is by homologous recombination in which the reverse transcriptase jumps from one template to the other. Formation of intrastrand stem-loop structures would be expected to influence the location and likelihood of the interstrand base-pairing of homologous regions. When naked RNA was used in vitro as a template for reverse transcriptase, two hot spots for recombination were found. However, if the acceptor strand (to which the transcriptase jumps) was allowed to bind NCp7, there was much more recombination, and the greatest increases were observed in areas where recombination had been relatively infrequent. A similar effect was seen with a different chaperone, Escherichia coli StpA, indicating that chaperone-mediated RNA folding (and unfolding) may be a general mechanism for more evenly promoting recombination.—BJ

Proc. Natl. Acad. Sci. U.S.A.97, 6385 (2000).

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