Peleg, Ofer;Trifonov, Edward;Bolshoy, Alexander - Hidden messages in the nef gene of HIV-1suggest a novel RNA secondary structure

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Title: Hidden messages in the nef gene of HIV-1suggest a novel RNA secondary structure	P118
Peleg, Ofer; Trifonov, Edward; Bolshoy, Alexander peleg@research.haifa.ac.il Institute of Evolution, University of Haifa, Haifa Israel

The coexistence of multiple codes in the genome of Human Immunodeficiency Virus type 1 (HIV-1) was analyzed. There are several well-known RNA secondary structures along the HIV-1 genome that play various functional roles during the virus life cycle. One of the best known is the rev responsive element (RRE), which interacts with the Rev transactivator protein [1, 2]. In elucidation of this structure the bioinformatics and RNA secondary structure prediction techniques had played a crucial role [3]. We explored factors constraining the variability of the virus genome primarily in relation to conserved RNA secondary structures overlapping coding sequences, and used a simple combination of algorithms for RNA secondary structure prediction based on nearest neighbor thermodynamic rules and statistical approach. In our previous study we applied this combination to a non-redundant data set of env nucleotide sequences, confirmed the conservative secondary structure of the Rev Responsive Element (RRE), and found a new RNA structure in the first conserved (C1) region of the env gene [4]. In this study we analyzed the variability of putative RNA secondary structures inside the nef gene of HIV-1 by applying these algorithms to a non-redundant data set of 104 nef sequences retrieved from Los Alamos HIV database, and predicted the existence of a novel functional RNA secondary structure in the b3 region of nef. The predicted RNA fold in the b3 region of nef appears in two forms, with different loop sizes. The loop of the first fold consists of 7 nucleotides (positions 494-500) with consensus UCAAGCU. It appeared in 82 out of 104 sequences (79%). The second fold has a 5 base loop (positions 495-499) with consensus CAAGC appearing in the other 22 sequences (21%). In general, sequence conservation in the fold with the larger loop is higher than in the other form. The difference in size between these two loops may reflect difference between respective counterparts in the hairpin recognition. This may also have an adaptive biological significance.

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[3] Le S-Y, Chen J, and Maizel J: Detection of unusual RNA folding regions in HIV and SIV sequences. Comput Appl Biosci 1991; 7:51-55.
[4] Peleg O., Brunak, S., Trifonov, E.N., Nevo, E. and Bolshoy A.: RNA Secondary Structure and Sequence Conservation in C1 Region of Human Immunodeficiency Virus Type 1 env Gene. AIDS Research and Human Retroviruses 2002; 18:867-878.