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

Nat Commun. 2020 Jan 9;11(1):148. doi: 10.1038/s41467-019-13942-4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Magnesium / chemistry
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Protein Binding
  • Protein Domains / physiology
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins / metabolism*
  • Scattering, Small Angle

Substances

  • CNBP protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Magnesium