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J Mol Biol. 2019 Apr 5;431(8):1592-1603. doi: 10.1016/j.jmb.2019.03.012. Epub 2019 Mar 16.

Phylogenetic Analysis with Improved Parameters Reveals Conservation in lncRNA Structures.

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Department of Chemistry, Yale University, New Haven, CT 06511, USA.
Department of Chemistry, Yale University, New Haven, CT 06511, USA; Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address:
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA. Electronic address:


The existence of evolutionary conservation in base pairing is strong evidence for functional elements of RNA structure, although available tools for rigorous identification of structural conservation are limited. R-scape is a recently developed program for statistical prediction of pairwise covariation from sequence alignments, but it initially showed limited utility on long RNAs, especially those of eukaryotic origin. Here we show that R-scape can be adapted for a more powerful analysis of structure conservation in long RNA molecules, including mammalian lncRNAs.


RNAalifold; conserved structure; covariation analysis; lncRNA structure; long non-coding RNAs

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