Nucleic Acids Research, 1988, Vol. 16, No. 11 5153-5168
© 1988
Articles |
Stability of RNA stem-loop structure and distribution of non-random structure in the human immunodeficiency virus (HIV-I)
Laboratory of Mathematical Biology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health Frederick, MD 21701, USA 1Shanghai Institute of Biochemistry, Chinese Academy of Sciences Shanghai 200031, China 2Advanced Scientific Computer Laboratory, Program Resources, Inc., NCI/FCRF Frederick, MD 21701, USA 3Laboratory of Cell and Molecular Structure, NCI/FCRF Frederick, MD 21701, USA
Received October 13, 1987. Revised December 11, 1987. Accepted December 11, 1987.
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' terminal 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 nucleotldes 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.
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