TY - JOUR
T1 - Structural basis for transcriptional start site control of HIV-1 RNA fate
AU - Brown, Joshua D.
AU - Kharytonchyk, Siarhei
AU - Chaudry, Issac
AU - Iyer, Aishwarya S.
AU - Carter, Hannah
AU - Becker, Ghazal
AU - Desai, Yash
AU - Glang, Lindsay
AU - Choi, Seung H.
AU - Singh, Karndeep
AU - Lopresti, Michael W.
AU - Orellana, Matthew
AU - Rodriguez, Tatiana
AU - Oboh, Ubiomo
AU - Hijji, Jana
AU - Ghinger, Frances Grace
AU - Stewart, Kailan
AU - Francis, Dillion
AU - Edwards, Bryce
AU - Chen, Patrick
AU - Case, David A.
AU - Telesnitsky, Alice
AU - Summers, Michael F.
N1 - Funding Information:
We thank HHMI staff at UMBC for technical assistance, C. Burnett (University of Michigan Medical School) for help with manuscript preparation, and R. Sprangers (University of Regensburg, Germany) for helpful suggestions. Funding: This research was supported by research grants from the National Institutes of Health (NIAID 8R01 AI50498 to M.F.S. and A.T., NIAID U54 AI150470 to A.T. and D.A.C.). J.D.B. was supported by NIH predoctoral fellowship F31 GM123803; M.L., K. Singh, M.O., T.R., and F.G.G. were supported by an NIGMS grant for enhancing minority access to research careers (MARC U*STAR 2T34 GM008663); M.O. and T.R. were supported by an HHMI undergraduate education grant; A.S.I., M.L., K. Singh, M.O., T.R., and F.G.G. were supported by the Meyerhoff Scholars
Publisher Copyright:
Copyright © 2020 The Authors,
PY - 2020/4/24
Y1 - 2020/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083899806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083899806&partnerID=8YFLogxK
U2 - 10.1126/science.aaz7959
DO - 10.1126/science.aaz7959
M3 - Article
C2 - 32327595
AN - SCOPUS:85083899806
SN - 0036-8075
VL - 368
SP - 413
EP - 417
JO - Science
JF - Science
IS - 6489
ER -