| Literature DB >> 32327595 |
Joshua D Brown1, Siarhei Kharytonchyk2, Issac Chaudry1, Aishwarya S Iyer1, Hannah Carter1, Ghazal Becker1, Yash Desai1, Lindsay Glang1, Seung H Choi1, Karndeep Singh1, Michael W Lopresti1, Matthew Orellana1, Tatiana Rodriguez1, Ubiomo Oboh1, Jana Hijji1, Frances Grace Ghinger1, Kailan Stewart1, Dillion Francis1, Bryce Edwards1, Patrick Chen1, David A Case3, Alice Telesnitsky4, Michael F Summers5.
Abstract
Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines (Cap1G, Cap2G, or Cap3G, respectively) that are either selected for packaging as genomes (Cap1G) or retained in cells as translatable messenger RNAs (mRNAs) (Cap2G and Cap3G). To understand how 5'-guanosine number influences fate, we probed the structures of capped HIV-1 leader RNAs by deuterium-edited nuclear magnetic resonance. The Cap1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping. The Cap2G and Cap3G transcripts adopt an alternate structure with an elongated central helix, exposed splice donor residues, and an accessible cap. Extensive remodeling, achieved at the energetic cost of a G-C base pair, explains how a single 5'-guanosine modifies the function of a ~9-kilobase HIV-1 transcript.Entities:
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Year: 2020 PMID： 32327595 PMCID： PMC7351118 DOI： 10.1126/science.aaz7959
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728