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Zinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution

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  • Doo Nam Kim

    (Theoretical Biology and Biophysics Group, Los Alamos National Laboratory)

  • Bernhard C. Thiel

    (Department of Theoretical Chemistry, University of Vienna)

  • Tyler Mrozowich

    (Alberta RNA Research & Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge)

  • Scott P. Hennelly

    (Theoretical Biology and Biophysics Group, Los Alamos National Laboratory
    New Mexico Consortium)

  • Ivo L. Hofacker

    (Department of Theoretical Chemistry, University of Vienna
    Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna)

  • Trushar R. Patel

    (Alberta RNA Research & Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge
    Cumming School of Medicine, University of Calgary
    Li Ka Shing Institute of Virology, University of Alberta)

  • Karissa Y. Sanbonmatsu

    (Theoretical Biology and Biophysics Group, Los Alamos National Laboratory
    New Mexico Consortium)

Abstract

Long non-coding RNAs (lncRNAs) constitute a significant fraction of the transcriptome, playing important roles in development and disease. However, our understanding of structure-function relationships for this emerging class of RNAs has been limited to secondary structures. Here, we report the 3-D atomistic structural study of epigenetic lncRNA, Braveheart (Bvht), and its complex with CNBP (Cellular Nucleic acid Binding Protein). Using small angle X-ray scattering (SAXS), we elucidate the ensemble of Bvht RNA conformations in solution, revealing that Bvht lncRNA has a well-defined, albeit flexible 3-D structure that is remodeled upon CNBP binding. Our study suggests that CNBP binding requires multiple domains of Bvht and the RHT/AGIL RNA motif. We show that RHT/AGIL, previously shown to interact with CNBP, contains a highly flexible loop surrounded by more ordered helices. As one of the largest RNA-only 3-D studies, the work lays the foundation for future structural studies of lncRNA-protein complexes.

Suggested Citation

  • Doo Nam Kim & Bernhard C. Thiel & Tyler Mrozowich & Scott P. Hennelly & Ivo L. Hofacker & Trushar R. Patel & Karissa Y. Sanbonmatsu, 2020. "Zinc-finger protein CNBP alters the 3-D structure of lncRNA Braveheart in solution," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13942-4
    DOI: 10.1038/s41467-019-13942-4
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