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Probing RNA Conformational Equilibria within the Functional Cellular Context.

Publication ,  Journal Article
Ganser, LR; Chu, C-C; Bogerd, HP; Kelly, ML; Cullen, BR; Al-Hashimi, HM
Published in: Cell Rep
February 25, 2020

Low-abundance short-lived non-native conformations referred to as excited states (ESs) are increasingly observed in vitro and implicated in the folding and biological activities of regulatory RNAs. We developed an approach for assessing the relative abundance of RNA ESs within the functional cellular context. Nuclear magnetic resonance (NMR) spectroscopy was used to estimate the degree to which substitution mutations bias conformational equilibria toward the inactive ES in vitro. The cellular activity of the ES-stabilizing mutants was used as an indirect measure of the conformational equilibria within the functional cellular context. Compensatory mutations that restore the ground-state conformation were used to control for changes in sequence. Using this approach, we show that the ESs of two regulatory RNAs from HIV-1, the transactivation response element (TAR) and the Rev response element (RRE), likely form in cells with abundances comparable to those measured in vitro, and their targeted stabilization may provide an avenue for developing anti-HIV therapeutics.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 25, 2020

Volume

30

Issue

8

Start / End Page

2472 / 2480.e4

Location

United States

Related Subject Headings

  • RNA Stability
  • Nucleic Acid Conformation
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells
  • Genes, env
  • Cellular Microenvironment
  • Cells
  • 31 Biological sciences
 

Citation

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Ganser, L. R., Chu, C.-C., Bogerd, H. P., Kelly, M. L., Cullen, B. R., & Al-Hashimi, H. M. (2020). Probing RNA Conformational Equilibria within the Functional Cellular Context. Cell Rep, 30(8), 2472-2480.e4. https://doi.org/10.1016/j.celrep.2020.02.004
Ganser, Laura R., Chia-Chieh Chu, Hal P. Bogerd, Megan L. Kelly, Bryan R. Cullen, and Hashim M. Al-Hashimi. “Probing RNA Conformational Equilibria within the Functional Cellular Context.Cell Rep 30, no. 8 (February 25, 2020): 2472-2480.e4. https://doi.org/10.1016/j.celrep.2020.02.004.
Ganser LR, Chu C-C, Bogerd HP, Kelly ML, Cullen BR, Al-Hashimi HM. Probing RNA Conformational Equilibria within the Functional Cellular Context. Cell Rep. 2020 Feb 25;30(8):2472-2480.e4.
Ganser, Laura R., et al. “Probing RNA Conformational Equilibria within the Functional Cellular Context.Cell Rep, vol. 30, no. 8, Feb. 2020, pp. 2472-2480.e4. Pubmed, doi:10.1016/j.celrep.2020.02.004.
Ganser LR, Chu C-C, Bogerd HP, Kelly ML, Cullen BR, Al-Hashimi HM. Probing RNA Conformational Equilibria within the Functional Cellular Context. Cell Rep. 2020 Feb 25;30(8):2472-2480.e4.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 25, 2020

Volume

30

Issue

8

Start / End Page

2472 / 2480.e4

Location

United States

Related Subject Headings

  • RNA Stability
  • Nucleic Acid Conformation
  • Humans
  • Hela Cells
  • HeLa Cells
  • HEK293 Cells
  • Genes, env
  • Cellular Microenvironment
  • Cells
  • 31 Biological sciences