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Albany 2001

category image Biomolecular
Stereodynamics
SUNY at Albany
June 19-23, 2001

Unusual folding of RNA chain within dimerization sites of avian retroviral RNA

The genome of all retroviruses is composed of two identical copies of RNA that dimerize near their 5'-ends. The dimerization of genomic RNA is an important step in the retroviral life cycle [1, 2, 3]. Here, we consider various RNA conformations and conformational switches in the vicinity of dimerization sites of avian retroviruses: pseudoknots, slipped-loop structures (SLS) [4, 5], kissing hairpins [6] and related conformations. Sequence analysis of more than 20 avian retroviruses revealed two SLS- compatible sites. In principle, these sequences can potentially form several alternative structures, including SLS. We used enzymatic probing of model RNA oligonucleotides to distinguish between the possible structures. One of the SLS-compatible sites overlaps with the dimerization initiation site and corresponds to nucleotides 237 ? 268 (avian sarcoma virus CT-10 numbering); the second one is located downstream and includes nucleotides 522-547. Probing experiments involved single- and double-strand specific RNases T1, U2, S1 and V1. Minimum-length oligonucleotide constructs corresponding to the site 1 of avian sarcoma virus CT-10 and avian leukosis virus HPRS-103 adopt bimolecular SLS conformations. However, probing of longer RNA fragments indicated that more stable kissing loop-loop interaction can compete with putative SLS. Possible roles of SLS, kissing hairpins and linear mismatch duplexes in the stabilization of the initial dimeric structure and in the conformational rearrangement of the mature dimer will be discussed. This work was supported in part by Fogarty International Research Collaboration Award 1 R03 TW01465-01 and State Support for Leading Scientific Schools, Grant No 00-15-97837 (Russia)

References and Footnotes
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  3. Polge E., Darlix J-L., Paoletti J. and Fosse P. J. Mol. Biol., 2000, 300, 41-56.
  4. Minyat E.E., Khomyakova E.B., Petrova M.V., Zdobnov E.M., Ivanov V.I., J. Biomolec. Struct. Dynam., 1995, 13, 523-527.
  5. Ulyanov N.B., Ivanov V.I., Minyat E.E., Khomyakova E.B., Petrova M.V., Lesiak K., James T.L. Biochemistry, 1998, 37, 12715-12726.
  6. Mujeeb A., Clever J.L., Billeci T.M., James T.L., Parslow T.G. Nat. Struct. Biol., 1998, 5, 432-436.

E.E. Minyat, A.D. Beniaminov, V.I. Ivanov, Z. Du (1), N.B. Ulyanov (1) and T.L. James (1)

The Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilova str., Moscow 119991, Russia,
(1) Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143-0446
E.E. Minyat Fax: (095)135-1405 e-mail: elvira@cmpv.phys.msu.su