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 59 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.
Visualizing the secondary and tertiary architectural domains of lnc RNA RepA
Creators
Fei Liu - Yale University
Srinivas Somarowthu - Yale University
Anna Marie Pyle - Yale University
Publication Details
Nature chemical biology, v 13(3)
Publisher
Springer Nature
Number of pages
10
Grant note
R01GM050313 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
R01GM50313 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Resource Type
Journal article
Language
English
Academic Unit
Biochemistry and Molecular Biology
Web of Science ID
WOS:000394431500010
Scopus ID
2-s2.0-85008618454
Other Identifier
991019167323904721
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