2009 August 6; 460(7256): 711–716. doi:10.1038/nature08237 | Joseph M. Watts, Kristen K. Dang, Robert J. Gorelick, Christopher W. Leonard, Julian W. Bess Jr., Ronald Swanstrom, Christina L. Burch, and Kevin M. Weeks
This study reports the single-nucleotide resolution structure of the entire HIV-1 genome using SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension) technology. The analysis reveals that the HIV-1 genome encodes protein structure at two levels: a linear relationship between RNA and protein primary sequences, and higher-order RNA structure that directly encodes protein tertiary structure through unstructured protein loops. The study identifies previously unknown regulatory motifs and organizational principles for unstructured RNA regions, such as the role of stable insulator helices in sequestering hypervariable regions. The findings suggest that extensive RNA structure may constitute an additional level of the genetic code, modulating ribosome elongation to promote native protein folding.This study reports the single-nucleotide resolution structure of the entire HIV-1 genome using SHAPE (selective 2′-hydroxyl acylation analyzed by primer extension) technology. The analysis reveals that the HIV-1 genome encodes protein structure at two levels: a linear relationship between RNA and protein primary sequences, and higher-order RNA structure that directly encodes protein tertiary structure through unstructured protein loops. The study identifies previously unknown regulatory motifs and organizational principles for unstructured RNA regions, such as the role of stable insulator helices in sequestering hypervariable regions. The findings suggest that extensive RNA structure may constitute an additional level of the genetic code, modulating ribosome elongation to promote native protein folding.