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PMID: 8331728 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The basic domain of Rev from human immunodeficiency virus type 1 specifically blocks the entry of U4/U6.U5 small nuclear ribonucleoprotein in spliceosome assembly.

Journal of virology ·Vol. 67 ·No. 8 ·1993-08-00 ·Pages 4769-76

Kjems J, Sharp PA

Abstract

Human immunodeficiency virus type 1 (HIV-1) encodes a regulatory protein, Rev, which is required for cytoplasmic expression of incompletely spliced viral mRNA. Rev binds to a cis-acting Rev-responsive element (RRE) located within the env region of HIV-1. It has previously been shown that a 17-amino-acid peptide, corresponding to the basic domain of Rev, specifically inhibited in vitro the splicing of mRNAs containing the RRE. In this reaction, the peptide acts after an ATP-dependent step in the spliceosome assembly resulting in an accumulation of a 45-50S splicing-deficient complex. Characterization of this complex revealed that the basic domain of Rev does not interfere with U1 small nuclear ribonucleoprotein binding but blocks the entry of U4, U5, and U6 small nuclear RNAs into the spliceosome. Binding of U2 small nuclear ribonucleoprotein was partially inhibited. The critical nature of the oligomeric structure of RRE has been investigated both in vitro and in vivo. Reporter genes that contained one, three, or six repeated-monomer high-affinity Rev binding sites (IIB) within an intron yielded a correlation among the oligomeric state of bound Rev; inhibition of splicing; ability to block the assembly of U4, U5, and U6 small nuclear RNAs in the spliceosome in vitro; and level of Rev response in vivo.

Related Genes
env
MeSH Terms
Base Sequence Blotting, Northern Gene Products, rev/biosynthesis,genetics,pharmacology Genes, env HIV-1/genetics,physiology Humans Molecular Sequence Data Nucleic Acid Conformation Peptide Fragments/pharmacology Plasmids Protein Binding RNA Precursors/genetics,metabolism RNA Splicing RNA, Messenger/genetics,metabolism RNA, Small Nuclear/metabolism RNA, Viral/genetics,metabolism Restriction Mapping Ribonucleoprotein, U4-U6 Small Nuclear/antagonists & inhibitors,metabolism Spliceosomes/drug effects,metabolism rev Gene Products, Human Immunodeficiency Virus
Chemicals
Gene Products, rev Peptide Fragments RNA Precursors RNA, Messenger RNA, Small Nuclear RNA, Viral Ribonucleoprotein, U4-U6 Small Nuclear rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kjems J
Department of Molecular Biology, University of Aarhus, Denmark.
Sharp P A
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49 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.8.4769-4776.1993
Published
1993-08-00
Pages
4769-76
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237863
Subset
IM
Grants
NIAID NIH HHS · AI32486 · United States
NCI NIH HHS · CA14051 · United States
NIGMS NIH HHS · GM34277 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.8.4769-4776.1993 PMC Full Text View journal details
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