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

Visualizing the secondary and tertiary architectural domains of lncRNA RepA.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA.
2
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
3
Department of Chemistry, Yale University, New Haven, Connecticut, USA.

Abstract

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.

PMID:
28068310
DOI:
10.1038/nchembio.2272
[Indexed for MEDLINE]

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