Gunnery, S., Green, S. R., Mathews, M. B. (December 1992) Tat-responsive region RNA of human immunodeficiency virus type 1 stimulates protein synthesis in vivo and in vitro: relationship between structure and function. Proc Natl Acad Sci U S A, 89 (23). pp. 11557-61. ISSN 0027-8424 (Print)0027-8424 (Linking)
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Abstract
The Tat-responsive region (TAR) sequence is present at the 5' end of human immunodeficiency virus 1 mRNAs and as a cytoplasmic form of 58-66 nucleotides. TAR RNA blocks the activation and autophosphorylation of the double-stranded RNA-activated protein kinase in vitro. We show here that TAR RNA also prevents the double-stranded RNA-mediated inhibition of translation in a cell-free system. Mutagenic and structural analyses of TAR RNA indicate that a stem of at least 14 base pairs is required for this activity, whereas the loop and bulge required for transactivation by Tat are dispensable. Truncation of the RNA to 68 nucleotides results in the loss of translational rescue ability, suggesting that the short cytoplasmic TAR RNA produced by viral transcription in vivo may not have the capability to suppress activation of the kinase. However, because longer TAR transcripts stimulate expression in a transient assay in vivo, the TAR structure at the 5' end of viral mRNAs could still exert this function in cis.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Base Sequence DNA Mutational Analysis *Gene Expression Regulation, Viral Gene Products, tat/*genetics HIV-1/*genetics Hydrogen Bonding In Vitro Techniques Molecular Sequence Data Nucleic Acid Conformation Phosphorylation *Protein Biosynthesis Protein Kinases/*metabolism RNA, Double-Stranded/genetics RNA, Messenger/genetics/ultrastructure RNA, Viral/*genetics Regulatory Sequences, Nucleic Acid Structure-Activity Relationship eIF-2 Kinase tat Gene Products, Human Immunodeficiency Virus |
| Subjects: | diseases & disorders > viral diseases > HIV bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA |
| CSHL Authors: | |
| Communities: | CSHL labs |
| Depositing User: | Matt Covey |
| Date: | 1 December 1992 |
| Date Deposited: | 22 Sep 2015 15:35 |
| Last Modified: | 09 Nov 2017 20:07 |
| PMCID: | PMC50591 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31854 |
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