Title |
Structural basis for transcriptional start site control of HIV-1 RNA fate
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Published in |
Science, April 2020
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DOI | 10.1126/science.aaz7959 |
Pubmed ID | |
Authors |
Joshua D Brown, Siarhei Kharytonchyk, Issac Chaudry, Aishwarya S Iyer, Hannah Carter, Ghazal Becker, Yash Desai, Lindsay Glang, Seung H Choi, Karndeep Singh, Michael W Lopresti, Matthew 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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 9 | 35% |
Australia | 4 | 15% |
France | 2 | 8% |
United Kingdom | 1 | 4% |
Belgium | 1 | 4% |
Russia | 1 | 4% |
Canada | 1 | 4% |
Unknown | 7 | 27% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 12 | 46% |
Scientists | 9 | 35% |
Science communicators (journalists, bloggers, editors) | 4 | 15% |
Practitioners (doctors, other healthcare professionals) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 90 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 33% |
Researcher | 13 | 14% |
Student > Doctoral Student | 7 | 8% |
Other | 4 | 4% |
Student > Postgraduate | 3 | 3% |
Other | 7 | 8% |
Unknown | 26 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 38 | 42% |
Immunology and Microbiology | 7 | 8% |
Agricultural and Biological Sciences | 5 | 6% |
Chemistry | 3 | 3% |
Medicine and Dentistry | 3 | 3% |
Other | 7 | 8% |
Unknown | 27 | 30% |