REVIEW: RNA Recognition and Regulation of HIV-1 Gene Expression by Viral Factor Tat

N. A. Naryshkin¹, M. J. Gait², and M. G. Ivanovskaya^1*

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-3181; E-mail: mgi@nuclacid.genebee.msu.su

²Medical Research Council, Laboratory of Molecular Biology, Hills Road CB2 2QH, Cambridge, UK; fax: (+44-1223) 41-2282; E-mail: mgkr@mrc-lmb.cam.ac.uk

^* To whom correspondence should be addressed.

Received September 23, 1997

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Viral transcription factor Tat is a small nuclear protein containing a large number of basic amino acids. The tat gene consists of two exons but only the first encoding 72-amino acid polypeptide is necessary for protein activity. Since the second exon is poorly conservative the total number of amino acids among Tat proteins from different strains of HIV-1 varies from 86 to 130. Tat protein acts as trans-activator of HIV genome transcription. It is absolutely required for viral functioning. Tat increases processivity of RNA-polymerase II by abolition of transcription blockade, which appears after polycondensation of the first 60-70 nucleotides of either HIV mRNA, i.e., it acts as antiterminator. For manifestation of its activity Tat specifically binds to the double stranded RNA fragment called TAR which is located at the 5'-terminus of all HIV mRNAs. The TAR structure contains a hairpin and a side loop. The Tat-binding region includes only a site of the loop; manifestation of Tat activity in vivo requires the full TAR and additional cellular co-factors.

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KEY WORDS: human immunodeficiency virus (HIV), Tat protein, transactivation, RNA--protein interaction

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