Structural basis for transcriptional start site control of HIV-1 RNA fate
Joshua D. Brown, Siarhei Kharytonchyk, Issac Chaudry, Aishwarya Iyer, Hannah M. Carter, Ghazal Becker, Yash Desai, Lindsay Glang, Seung Hyuk Choi, Karndeep Singh, Michael Lopresti, Matthew R. Orellana, Tatiana Rodriguez, Ubiomo Oboh, Jana Hijji, Frances Grace Ghinger, Kailan Stewart, Dillion Francis, Bryce Edwards, Patrick Chen, David A. Case, Alice Telesnitsky, Michael F. Summers
Abstract
One guanosine determines transcript fate Transcripts of the HIV-1 RNA genome can be either spliced and translated into viral proteins or packaged into new virions as a progeny genome. The path taken depends on whether the transcript contains one guanosine at the 5′ terminus (1G) rather than two or three (2G or 3G). Brown et al. used nuclear magnetic resonance spectroscopy to show that 1G transcripts adopt a dimeric structure that sequesters a terminal cap required for translation and splicing but exposes sites that bind to the HIV-1 Gag protein, which recruits the genome during viral assembly. Conversely, 2G or 3G transcripts have the cap accessible, but Gag-binding sites are sequestered. Therefore, a single guanosine acts as a conformational switch to determine the fate of HIV-1 transcripts. Science , this issue p. 413