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SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells.

Publication ,  Journal Article
Smola, MJ; Christy, TW; Inoue, K; Nicholson, CO; Friedersdorf, M; Keene, JD; Lee, DM; Calabrese, JM; Weeks, KM
Published in: Proc Natl Acad Sci U S A
September 13, 2016

The 18-kb Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation during female eutherian mammalian development. Global structural architecture, cell-induced conformational changes, and protein-RNA interactions within Xist are poorly understood. We used selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) to examine these features of Xist at single-nucleotide resolution both in living cells and ex vivo. The Xist RNA forms complex well-defined secondary structure domains and the cellular environment strongly modulates the RNA structure, via motifs spanning one-half of all Xist nucleotides. The Xist RNA structure modulates protein interactions in cells via multiple mechanisms. For example, repeat-containing elements adopt accessible and dynamic structures that function as landing pads for protein cofactors. Structured RNA motifs create interaction domains for specific proteins and also sequester other motifs, such that only a subset of potential binding sites forms stable interactions. This work creates a broad quantitative framework for understanding structure-function interrelationships for Xist and other lncRNAs in cells.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 13, 2016

Volume

113

Issue

37

Start / End Page

10322 / 10327

Location

United States

Related Subject Headings

  • X Chromosome Inactivation
  • X Chromosome
  • RNA-Binding Proteins
  • RNA, Long Noncoding
  • Nucleic Acid Conformation
  • Mutation
  • Mice
  • Female
  • Animals
  • Acylation
 

Citation

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Smola, M. J., Christy, T. W., Inoue, K., Nicholson, C. O., Friedersdorf, M., Keene, J. D., … Weeks, K. M. (2016). SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells. Proc Natl Acad Sci U S A, 113(37), 10322–10327. https://doi.org/10.1073/pnas.1600008113
Smola, Matthew J., Thomas W. Christy, Kaoru Inoue, Cindo O. Nicholson, Matthew Friedersdorf, Jack D. Keene, David M. Lee, J Mauro Calabrese, and Kevin M. Weeks. “SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells.Proc Natl Acad Sci U S A 113, no. 37 (September 13, 2016): 10322–27. https://doi.org/10.1073/pnas.1600008113.
Smola MJ, Christy TW, Inoue K, Nicholson CO, Friedersdorf M, Keene JD, et al. SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10322–7.
Smola, Matthew J., et al. “SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells.Proc Natl Acad Sci U S A, vol. 113, no. 37, Sept. 2016, pp. 10322–27. Pubmed, doi:10.1073/pnas.1600008113.
Smola MJ, Christy TW, Inoue K, Nicholson CO, Friedersdorf M, Keene JD, Lee DM, Calabrese JM, Weeks KM. SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10322–10327.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 13, 2016

Volume

113

Issue

37

Start / End Page

10322 / 10327

Location

United States

Related Subject Headings

  • X Chromosome Inactivation
  • X Chromosome
  • RNA-Binding Proteins
  • RNA, Long Noncoding
  • Nucleic Acid Conformation
  • Mutation
  • Mice
  • Female
  • Animals
  • Acylation