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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Structural aspects of non-enzymatic recombination in viral RNA

Recombination is a significant source of genetic variation amongst RNA viruses and may occur even in the absence of enzymes (Chetverina et al., 1999). Non-enzymatic recombination remains more enigmatic than its enzyme-mediated counterpart and the structural rules by which it occurs are still largely unknown. Recent studies of non-enzymatic recombination, between fragments of human immunodeficiency virus 1 (HIV-1) RNA and human influenza A virus RNA (M2-RNA) (Nechaev et al., 2009), have indicated patterns in the sequences of recombinants, alluding to particular secondary structural motifs.

The 3D structural arrangements of such motifs may provide clues which will help to elucidate the mechanisms of non-enzymatic RNA recombination. Here we aim to investigate the 3D structures of recombinant RNA molecules in an attempt to uncover some of the structural rules underpinning non-enzymatic recombination in viral RNAs. Molecular Dynamics studies, focusing on the area surrounding the ligation site, have indicated multiple opportunities for recombination between model RNAs. Our results also suggest a preference in product formation, which reflects the experimental findings of Lutay et al. (2007).

Understanding the fundamental principles of these molecular interactions and regulatory mechanisms may provide insights into whether non-enzymatic recombination may have played a role in promoting genetic variation in a prebiotic "RNA world". Recombination is a contributing factor to the rapid evolution of viruses and the emergence of new, pathogenic strains. As such, this knowledge may also influence future strategies for the prevention and treatment of pathogenic viral diseases.

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Figure 1: (a) 3D structure of model recombination partners; (b) Distance between terminal groups of nucleotides at the ligation site of model RNAs; (c) Opportunities for recombination between model RNAs during 100ns MD simulation.

This research has been supported by the BBSRC. Grant ref: BB/J014478/1

References
    Chetverina, H. V., Demidenko, A. A., Ugarov, V. I. & Chetverin, A. B. (1999) Spontaneous rearrangements in RNA sequences. Febs Letters 450, 89-94.

    Nechaev, S. Y., Lutay, A. V., Vlassov, V. V. & Zenkova, M. A. (2009) Non-Enzymatic Template-Directed Recombination of RNAs. International Journal of Molecular Sciences 10 (4), 1788-1807.

    Lutay, A. V., Zenkova, M. A., & Vlassov, V. V. (2007). Nonenzymatic recombination of RNA: Possible mechanism for the formation of novel sequences. Chemistry & Biodiversity, 4(4), 762-7.


Catherine Watson*1
Yaroslav Staroseletz2
Marina A. Zenkova2
Richard Bryce1
Elena V. Bichenkova1

1 Manchester Pharmacy School
University of Manchester
UK, M13 9PT
2Institute of Chemical Biology and Fundamental Medicine
SB RAS
8 Laurentyev Avenue
630090, Novosibirsk, Russia

Ph: (+44) 161 275 2401
catherine.watson@manchester.ac.uk