Stability of RNA stem-loop structure and distribution of non-random structure in the human immunodeficiency virus (HIV-I)

Shu-Yun Le, Jih-H Chen, Michael J. Braun, Matthew A. Gonda, Jacob V. Maizel
1988 Nucleic Acids Research  
The stability of potential RNA stem-loop structures in human immunodeficiency virus isolates, HTLV-III and ARV, has been calculated, and the relevance to the local significant secondary structures in the sequence has been tested statistically using a Monte Carlo simulation method. Potentially significant structures exist in the 5'non-coding region, the boundary regions between the protein coding frames, and the 3' non-coding region. The locally optimal secondary structure occurring in the 5'
more » ... minal region has been assessed using different overlapping segment sizes and the Monte Carlo method. The results show that the most favorable structure for the 5' mRNA leader sequence of HIV has two stem-loops folded at nucleotides 5-104 in the R region (stem-loop I, 5-54 and stem-loop II, 58-104). A large fluctuation of segment score of the local optimal secondary structure also occurs in the boundary between the exterior glycosylated protein or outer membrane protein and transmembrane protein coding region. This finding is surprising since no RNA signals or RNA processing are expected to occur at this site. In addition, regions of the genome predicted to have significantly more open structure at the RNA level correlate closely with hypervariable sites found in these viral genomes. The possible importance of local secondary structure to the biological function of the human immunodeficiency virus genome is discussed. that the human immunodeficiency virus (HIV-I), the causative agent of AIDS, has a complex genetic structure (1) (2) (3) (4) (5) (6) (7) (8) 26 ). An important clue in understanding the differential regulation of HIV gene expression was provided by the identification of a trans-activator gene(tat) in the HIV genome (9-12). Recently, Cullen(13) presented data suggesting that tat functions in two distinct ways to increase gene expression driven by the HIV long terminal repeat (LTR): first, by enhancing the steady state level © I R L Press Limited, Oxford, England. 5153
doi:10.1093/nar/16.11.5153 pmid:3387221 pmcid:PMC336724 fatcat:dxbudqeh7ffwbfttlne6hudaja