Visualizing the secondary and tertiary architectural domains of lncRNA RepA

Nat Chem Biol. 2017 Mar;13(3):282-289. doi: 10.1038/nchembio.2272. Epub 2017 Jan 9.


Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, although its exact role is poorly understood. To gain insight into the molecular mechanism of RepA and Xist, we determined a complete phylogenetically validated secondary-structural map of RepA through SHAPE and DMS chemical probing of a homogeneously folded RNA in vitro. We combined UV-cross-linking experiments with RNA modeling methods to produce a three-dimensional model of RepA functional domains demonstrating that tertiary architecture exists within lncRNA molecules and occurs within specific functional modules. This work provides a foundation for understanding of the evolution and functional properties of RepA and Xist and offers a framework for exploring architectural features of other lncRNAs.

Publication types

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

MeSH terms

  • Animals
  • Mice
  • Models, Molecular
  • Nucleic Acid Conformation*
  • RNA, Long Noncoding / chemistry*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism


  • RNA, Long Noncoding