PMID- 31068467
OWN - NLM
STAT- MEDLINE
DCOM- 20200326
LR  - 20200613
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 116
IP  - 21
DP  - 2019 May 21
TI  - Intrinsic conformational dynamics of the HIV-1 genomic RNA 5'UTR.
PG  - 10372-10381
LID - 10.1073/pnas.1902271116 [doi]
AB  - The highly conserved 5' untranslated region (5'UTR) of the HIV-1 RNA genome is 
      central to the regulation of virus replication. NMR and biochemical experiments 
      support a model in which the 5'UTR can transition between at least two 
      conformational states. In one state the genome remains a monomer, as the 
      palindromic dimerization initiation site (DIS) is sequestered via base pairing to 
      upstream sequences. In the second state, the DIS is exposed, and the genome is 
      competent for kissing loop dimerization and packaging into assembling virions 
      where an extended dimer is formed. According to this model the conformation of 
      the 5'UTR determines the fate of the genome. In this work, the dynamics of this 
      proposed conformational switch and the factors that regulate it were probed using 
      multiple single-molecule and in-gel ensemble FRET assays. Our results show that 
      the HIV-1 5'UTR intrinsically samples conformations that are stabilized by both 
      viral and host factor binding. Annealing of tRNA(Lys3), the primer for initiation 
      of reverse transcription, can promote the kissing dimer but not the extended 
      dimer. In contrast, HIV-1 nucleocapsid (NC) promotes formation of the extended 
      dimer in both the absence and presence of tRNA(Lys3) Our data are consistent with 
      an ordered series of events that involves primer annealing, genome dimerization, 
      and virion assembly.
CI  - Copyright (c) 2019 the Author(s). Published by PNAS.
FAU - Brigham, Benjamin S
AU  - Brigham BS
AD  - Department of Molecular Biology and Microbiology, Tufts University School of 
      Medicine, Boston, MA 02111.
AD  - Program in Cellular, Molecular, and Developmental Biology, Sackler School of 
      Graduate Biomedical Sciences, Tufts University, Boston, MA 02111.
FAU - Kitzrow, Jonathan P
AU  - Kitzrow JP
AD  - Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 
      43210.
AD  - Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
AD  - Center for RNA Biology, The Ohio State University, Columbus, OH 43210.
FAU - Reyes, Joshua-Paolo C
AU  - Reyes JC
AD  - Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 
      43210.
AD  - Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
AD  - Center for RNA Biology, The Ohio State University, Columbus, OH 43210.
FAU - Musier-Forsyth, Karin
AU  - Musier-Forsyth K
AD  - Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 
      43210; musier-forsyth.1@osu.edu james.munro@tufts.edu.
AD  - Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210.
AD  - Center for RNA Biology, The Ohio State University, Columbus, OH 43210.
FAU - Munro, James B
AU  - Munro JB
AUID- ORCID: 0000-0001-7634-4633
AD  - Department of Molecular Biology and Microbiology, Tufts University School of 
      Medicine, Boston, MA 02111; musier-forsyth.1@osu.edu james.munro@tufts.edu.
AD  - Program in Cellular, Molecular, and Developmental Biology, Sackler School of 
      Graduate Biomedical Sciences, Tufts University, Boston, MA 02111.
LA  - eng
GR  - R21 AI136711/AI/NIAID NIH HHS/United States
GR  - P50 GM082251/GM/NIGMS NIH HHS/United States
GR  - T32 GM118291/GM/NIGMS NIH HHS/United States
GR  - U54 GM103368/GM/NIGMS NIH HHS/United States
GR  - R01 GM065056/GM/NIGMS NIH HHS/United States
GR  - P50 AI150481/AI/NIAID NIH HHS/United States
GR  - U54 AI150472/AI/NIAID NIH HHS/United States
GR  - U54 GM103297/GM/NIGMS NIH HHS/United States
GR  - R01 GM113887/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190508
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Viral)
RN  - 9014-25-9 (RNA, Transfer)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Base Pairing/genetics
MH  - Dimerization
MH  - Genome, Viral/*genetics
MH  - Genomics/methods
MH  - HIV-1/*genetics
MH  - Nucleic Acid Conformation
MH  - Nucleocapsid/genetics
MH  - RNA, Transfer/genetics
MH  - RNA, Viral/*genetics
MH  - Virion/genetics
MH  - Virus Assembly/genetics
MH  - Virus Replication/genetics
PMC - PMC6534999
OTO - NOTNLM
OT  - 5' untranslated region
OT  - HIV-1
OT  - RNA conformational dynamics
OT  - in-gel FRET
OT  - single-molecule FRET
COIS- The authors declare no conflict of interest.
EDAT- 2019/05/10 06:00
MHDA- 2020/03/27 06:00
PMCR- 2019/05/08
CRDT- 2019/05/10 06:00
PHST- 2019/05/10 06:00 [pubmed]
PHST- 2020/03/27 06:00 [medline]
PHST- 2019/05/10 06:00 [entrez]
PHST- 2019/05/08 00:00 [pmc-release]
AID - 1902271116 [pii]
AID - 201902271 [pii]
AID - 10.1073/pnas.1902271116 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2019 May 21;116(21):10372-10381. doi: 
      10.1073/pnas.1902271116. Epub 2019 May 8.