An unusual topological structure of the HIV-1 Rev response element.
Nuclear export of unspliced and singly spliced viral mRNA is a critical step in the HIV life cycle. The structural basis by which the virus selects its own mRNA among more abundant host cellular RNAs for export has been a mystery for more than 25 years. Here, we describe an unusual topological structure that the virus uses to recognize its own mRNA. The viral Rev response element (RRE) adopts an "A"-like structure in which the two legs constitute two tracks of binding sites for the viral Rev protein and position the two primary known Rev-binding sites ~55 Å apart, matching the distance between the two RNA-binding motifs in the Rev dimer. Both the legs of the "A" and the separation between them are required for optimal RRE function. This structure accounts for the specificity of Rev for the RRE and thus the specific recognition of the viral RNA.
Protein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Xianyang
X
Fang
Jinbu
J
Wang
Ina P
IP
O'Carroll
Michelle
M
Mitchell
Xiaobing
X
Zuo
Yi
Y
Wang
Ping
P
Yu
Yu
Y
Liu
Jason W
JW
Rausch
Marzena A
MA
Dyba
Jørgen
J
Kjems
Charles D
CD
Schwieters
Soenke
S
Seifert
Randall E
RE
Winans
Norman R
NR
Watts
Stephen J
SJ
Stahl
Paul T
PT
Wingfield
R Andrew
RA
Byrd
Stuart F J
SF
Le Grice
Alan
A
Rein
Yun-Xing
YX
Wang
D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus