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Related Experiment Videos

HIV-1 tat trans-activation requires the loop sequence within tar.

S Feng1, E C Holland

  • 1Department of Biochemistry, Stanford University Medical Center, California 94305.

Nature
|July 14, 1988
PubMed
Summary

The human immunodeficiency virus (HIV-1) tat protein is essential for viral replication. Nucleotide substitution experiments reveal that the tat protein requires a specific RNA hairpin structure in the tar region for trans-activation.

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Area of Science:

  • Molecular Biology
  • Virology
  • Genetics

Background:

  • Human immunodeficiency virus type 1 (HIV-1) causes AIDS, and its tat protein is crucial for viral gene expression.
  • Tat protein acts in trans to significantly upregulate all HIV-1 genes, indicating its essential role in viral replication.
  • The cis-acting site for tat trans-activation, known as tar, is located in the R region of the HIV-1 long terminal repeat (LTR).

Purpose of the Study:

  • To investigate the structural requirements of the tar RNA sequence for tat protein-mediated trans-activation.
  • To determine the role of a specific RNA hairpin structure within the tar region in facilitating HIV-1 gene expression.

Main Methods:

  • Performed nucleotide substitution experiments within the tar sequence of the HIV-1 LTR.

Related Experiment Videos

  • Analyzed the impact of these substitutions on tat protein-mediated trans-activation.
  • Investigated the potential for RNA secondary structure formation, specifically a stem-loop, within the tar region.

    • Main Results:

    • The RNA sequence between +1 and +59 of the HIV-1 LTR can form an extensive stem-loop secondary structure.
    • Nucleotide substitution experiments demonstrated that tat trans-activation is dependent on the presentation of the specific sequence +30CUGGG+34.
    • This critical sequence must be located within the loop of an RNA hairpin structure for effective trans-activation.

    Conclusions:

    • Tat trans-activation of HIV-1 gene expression is critically dependent on the formation of a specific RNA hairpin structure in the tar region.
    • The sequence +30CUGGG+34 within the tar hairpin loop is essential for mediating the trans-activation function of the tat protein.
    • Understanding these structural requirements provides insights into HIV-1 replication mechanisms and potential therapeutic targets.