A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction.
Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR, present in the proviral long terminal repeat (LTR) and at the 5' end of viral mRNAs. We have shown that Tat potentiates the expression of TAR-containing RNAs, but only when Tat and the TAR-containing RNA are present in the nucleus. We now show that a small change in the TAR loop abolishes nuclear potentiation by Tat. Furthermore, the HIV-1 U3 region induces expression incompetence in mRNA synthesized by this promoter. RNAs of identical structure are, however, translated efficiently when produced from the CMV-IE promoter. The Tat-TAR system appears, therefore, to rescue the expression potential of HIV-1 LTR-directed RNA.
Virus Molecular Biology Group, Department of Biochemistry, Oxford, United Kingdom.
M
M
Braddock
A M
AM
Thorburn
A
A
Chambers
G D
GD
Elliott
G J
GJ
Anderson
A J
AJ
Kingsman
S M
SM
Kingsman
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002472:Cell Transformation, Viral; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D015345:Oligonucleotide Probes; D009865:Oocytes / Q000502:physiology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011533:Proviruses / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D013698:Templates, Genetic; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication; D014982:Xenopus laevis; D054322:tat Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015696:Gene Products, tat; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus