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SHAPE analysis of the FIV Leader RNA reveals a structural switch potentially controlling viral packaging and genome dimerization

  1. Author:
    Kenyon, J. C.
    Tanner, S. J.
    Legiewicz, M.
    Phillip, P. S.
    Rizvi, T. A.
    Le Grice, S. F. J.
    Lever, A. M. L.

  2. Author Address

    [Kenyon, JC; Tanner, SJ; Lever, AML] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England. [Legiewicz, M; Le Grice, SFJ] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Phillip, PS; Rizvi, TA] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Microbiol & Immunol, Al Ain, U Arab Emirates.;Lever, AML (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Med, Box 157,Level 5,Hills Rd, Cambridge CB2 0QQ, England;amll1@medschl.cam.ac.uk
    1. Year: 2011
    2. Date: Aug
  2. Journal: Nucleic Acids Research
    1. 39
    2. 15
    3. Pages: 6692-6704
  4. Type of Article: Article
  5. ISSN: 0305-1048
  1. Abstract:

    Feline immunodeficiency virus (FIV) infects many species of cat, and is related to HIV, causing a similar pathology. High-throughput selective 2' hydroxyl acylation analysed by primer extension (SHAPE), a technique that allows structural interrogation at each nucleotide, was used to map the secondary structure of the FIV packaging signal RNA. Previous studies of this RNA showed four conserved stem-loops, extensive long-range interactions (LRIs) and a small, palindromic stem-loop (SL5) within the gag open reading frame (ORF) that may act as a dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Our analyses of wild-type (wt) and mutant RNAs suggest that although the four conserved stem-loops are static structures, the 5' and 3' regions previously shown to form LRI also adopt an alternative, yet similarly conserved conformation, in which the putative DIS is occluded, and which may thus favour translational and splicing functions over encapsidation. SHAPE and in vitro dimerization assays were used to examine SL5 mutants. Dimerization contacts appear to be made between palindromic loop sequences in SL5. As this stem-loop is located within the gag ORF, recognition of a dimeric RNA provides a possible mechanism for the specific packaging of genomic over spliced viral RNAs.

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External Sources

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  2. DOI: 10.1093/nar/gkr252
  3. View record in Web of Science®
  4. WOS: 000294555800039

Library Notes

  1. Fiscal Year: FY2010-2011
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