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

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Kim, Doo N.
Thiel, Bernhard C.
Mrozowich, Tyler
Hennelly, Scott P.
Hofacker, Ivo L.
Patel, Trushar R.
Sanbonmatsu, Karissa Y.
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Nature Portfolio
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.
Open access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
Biophysical chemistry , Biophysics , Computational biophysics , Molecular biophysics , RNA , IncRNA , 3-D studies
Kim, D. N., Thiel, B. C., Mrozowich, T., Hennelly, S. P., Hofacker, I. L., Patel, T. R., & Sanbonmatsu, K. Y. (2020). Zinc-finger protein CNBP alters the 3-D structure of IncRNA Braveheart in solution. Nature Communications, 11, Article 148. https://doi.org/10.1038/s41467-019-13942-4