Determination of the conformational ensemble of the TAR RNA by X-ray scattering interferometry

Shi, Xuesong; Walker, Peter; Harbury, Pehr B.; Herschlag, Daniel

doi:10.1093/nar/gkw1352

Determination of the conformational ensemble of the TAR RNA by X-ray scattering interferometry

Journal Article · Fri Jan 20 00:00:00 EST 2017 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkw1352· OSTI ID:1625552

Shi, Xuesong ^[1]; Walker, Peter ^[2]; Harbury, Pehr B. ^[3]; Herschlag, Daniel ^[4]

Stanford Univ., CA (United States). Dept. of Biochemistry; DOE/OSTI
Stanford Univ., CA (United States). Protein and Nucleic Acids Facility
Stanford Univ., CA (United States). Dept. of Biochemistry; Stanford Univ., CA (United States). ChEM-H
Stanford Univ., CA (United States). Dept. of Biochemistry; Stanford Univ., CA (United States). ChEM-H; Stanford Univ., CA (United States). Dept. of Chemistry; Stanford Univ., CA (United States). Dept. of Chemical Engineering

The conformational ensembles of structured RNA’s are crucial for biological function, but they remain difficult to elucidate experimentally. We demonstrate with HIV-1 TAR RNA that X-ray scattering interferometry (XSI) can be used to determine RNA conformational ensembles. X-ray scattering interferometry (XSI) is based on site-specifically labeling RNA with pairs of heavy atom probes, and precisely measuring the distribution of inter-probe distances that arise from a heterogeneous mixture of RNA solution structures. We show that the XSI-based model of the TAR RNA ensemble closely resembles an independent model derived from NMR-RDC data. Further, we show how the TAR RNA ensemble changes shape at different salt concentrations. Finally, we demonstrate that a single hybrid model of the TAR RNA ensemble simultaneously fits both the XSI and NMR-RDC data set and show that XSI can be combined with NMRRDC to further improve the quality of the determined ensemble. The results suggest that XSI-RNA will be a powerful approach for characterizing the solution conformational ensembles of RNAs and RNA-protein complexes under diverse solution conditions.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1625552

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 8 Vol. 45; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (31)

Review NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings Getz, Melissa; Sun, Xiaoyan; Casiano-Negroni, Anette Biopolymers, Vol. 86, Issue 5-6 https://doi.org/10.1002/bip.20765	journal	January 2007
Bulge-Induced Bends in RNA: Quantification by Transient Electric Birefringence Zacharias, Martin; Hagerman, Paul J. Journal of Molecular Biology, Vol. 247, Issue 3 https://doi.org/10.1006/jmbi.1995.0155	journal	March 1995
Major groove width variations in RNA structures determined by NMR and impact of 13C residual chemical shift anisotropy and 1H–13C residual dipolar coupling on refinement Tolbert, Blanton S.; Miyazaki, Yasuyuki; Barton, Shawn Journal of Biomolecular NMR, Vol. 47, Issue 3 https://doi.org/10.1007/s10858-010-9424-x	journal	June 2010
Distance distribution in a dye-linked oligonucleotide determined by time-resolved fluorescence energy transfer Hochstrasser, Remo A.; Chen, Shiow-Meei; Millar, David P. Biophysical Chemistry, Vol. 45, Issue 2, p. 133-141 https://doi.org/10.1016/0301-4622(92)87005-4	journal	December 1992
Toward a Consensus View of Duplex RNA Flexibility Faustino, Ignacio; Pérez, Alberto; Orozco, Modesto Biophysical Journal, Vol. 99, Issue 6 https://doi.org/10.1016/j.bpj.2010.06.061	journal	September 2010
A Decade of Riboswitches Serganov, Alexander; Nudler, Evgeny Cell, Vol. 152, Issue 1-2 https://doi.org/10.1016/j.cell.2012.12.024	journal	January 2013
Unveiling Inherent Degeneracies in Determining Population-Weighted Ensembles of Interdomain Orientational Distributions Using NMR Residual Dipolar Couplings: Application to RNA Helix Junction Helix Motifs Yang, Shan; Al-Hashimi, Hashim M. The Journal of Physical Chemistry B, Vol. 119, Issue 30 https://doi.org/10.1021/acs.jpcb.5b03859	journal	July 2015
A General Method for Constructing Atomic-Resolution RNA Ensembles using NMR Residual Dipolar Couplings: The Basis for Interhelical Motions Revealed Salmon, Loïc; Bascom, Gavin; Andricioaei, Ioan Journal of the American Chemical Society, Vol. 135, Issue 14 https://doi.org/10.1021/ja400920w	journal	March 2013
Modulating RNA Alignment Using Directional Dynamic Kinks: Application in Determining an Atomic-Resolution Ensemble for a Hairpin using NMR Residual Dipolar Couplings Salmon, Loïc; Giambaşu, George M.; Nikolova, Evgenia N. Journal of the American Chemical Society, Vol. 137, Issue 40 https://doi.org/10.1021/jacs.5b07229	journal	September 2015
The solution structural ensembles of RNA kink-turn motifs and their protein complexes Shi, Xuesong; Huang, Lin; Lilley, David M. J. Nature Chemical Biology, Vol. 12, Issue 3 https://doi.org/10.1038/nchembio.1997	journal	January 2016
Measuring similarity between dynamic ensembles of biomolecules Yang, Shan; Salmon, Loïc; Al-Hashimi, Hashim M. Nature Methods, Vol. 11, Issue 5 https://doi.org/10.1038/nmeth.2921	journal	April 2014
Structurally conserved five nucleotide bulge determines the overall topology of the core domain of human telomerase RNA Zhang, Q.; Kim, N. -K.; Peterson, R. D. Proceedings of the National Academy of Sciences, Vol. 107, Issue 44 https://doi.org/10.1073/pnas.1013269107	journal	October 2010
Topology Links RNA Secondary Structure with Global Conformation, Dynamics, and Adaptation Bailor, Maximillian H.; Sun, Xiaoyan; Al-Hashimi, Hashim M. Science, Vol. 327, Issue 5962 https://doi.org/10.1126/science.1181085	journal	January 2010
A Molecular Ruler for Measuring Quantitative Distance Distributions Mathew-Fenn, Rebecca S.; Das, Rhiju; Silverman, Joshua A. PLoS ONE, Vol. 3, Issue 10 https://doi.org/10.1371/journal.pone.0003229	journal	October 2008
RNA-guided assembly of Rev-RRE nuclear export complexes Bai, Yun; Tambe, Akshay; Zhou, Kaihong eLife, Vol. 3 https://doi.org/10.7554/elife.03656	journal	August 2014
NMR Studies of Biomolecular Dynamics and Structural Plasticity Using Residual Dipolar Couplings Tolman, Joel R.; Al-Hashimi, Hashim M. Annual Reports on NMR Spectroscopy https://doi.org/10.1016/S0066-4103(03)51003-1	book	January 2003
Constructing ensembles for intrinsically disordered proteins Fisher, Charles K.; Stultz, Collin M. Current Opinion in Structural Biology, Vol. 21, Issue 3 https://doi.org/10.1016/j.sbi.2011.04.001	journal	June 2011
The spliceosome: disorder and dynamics defined Chen, Weijun; Moore, Melissa J. Current Opinion in Structural Biology, Vol. 24 https://doi.org/10.1016/j.sbi.2014.01.009	journal	February 2014
Absolute Intramolecular Distance Measurements with Angstrom-Resolution Using Anomalous Small-Angle X-ray Scattering Zettl, Thomas; Mathew, Rebecca S.; Seifert, Sönke Nano Letters, Vol. 16, Issue 9 https://doi.org/10.1021/acs.nanolett.6b01160	journal	June 2016
Probing Na ⁺ -Induced Changes in the HIV-1 TAR Conformational Dynamics Using NMR Residual Dipolar Couplings: New Insights into the Role of Counterions and Electrostatic Interactions in Adaptive Recognition ^† Casiano-Negroni, Anette; Sun, Xiaoyan; Al-Hashimi, Hashim M. Biochemistry, Vol. 46, Issue 22 https://doi.org/10.1021/bi700335n	journal	June 2007
Visualizing spatially correlated dynamics that directs RNA conformational transitions Zhang, Qi; Stelzer, Andrew C.; Fisher, Charles K. Nature, Vol. 450, Issue 7173 https://doi.org/10.1038/nature06389	journal	December 2007
Functional complexity and regulation through RNA dynamics Dethoff, Elizabeth A.; Chugh, Jeetender; Mustoe, Anthony M. Nature, Vol. 482, Issue 7385 https://doi.org/10.1038/nature10885	journal	February 2012
Inter-helical conformational preferences of HIV-1 TAR-RNA from maximum occurrence analysis of NMR data and molecular dynamics simulations Andrałojć, Witold; Ravera, Enrico; Salmon, Loïc Physical Chemistry Chemical Physics, Vol. 18, Issue 8 https://doi.org/10.1039/C5CP03993B	journal	January 2016
Structural ensemble and microscopic elasticity of freely diffusing DNA by direct measurement of fluctuations Shi, X.; Herschlag, D.; Harbury, P. A. B. Proceedings of the National Academy of Sciences, Vol. 110, Issue 16 https://doi.org/10.1073/pnas.1218830110	journal	April 2013
DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals Hura, G. L.; Tsai, C. -L.; Claridge, S. A. Proceedings of the National Academy of Sciences, Vol. 110, Issue 43 https://doi.org/10.1073/pnas.1308595110	journal	October 2013
From a structural average to the conformational ensemble of a DNA bulge Shi, X.; Beauchamp, K. A.; Harbury, P. B. Proceedings of the National Academy of Sciences, Vol. 111, Issue 15 https://doi.org/10.1073/pnas.1317032111	journal	March 2014
A 1.3-A resolution crystal structure of the HIV-1 trans-activation response region RNA stem reveals a metal ion-dependent bulge conformation Ippolito, J. A.; Steitz, T. A. Proceedings of the National Academy of Sciences, Vol. 95, Issue 17 https://doi.org/10.1073/pnas.95.17.9819	journal	August 1998
Remeasuring the Double Helix Mathew-Fenn, R. S.; Das, R.; Harbury, P. A. B. Science, Vol. 322, Issue 5900 https://doi.org/10.1126/science.1158881	journal	October 2008
DEER Distance Measurements on Proteins Jeschke, Gunnar Annual Review of Physical Chemistry, Vol. 63, Issue 1 https://doi.org/10.1146/annurev-physchem-032511-143716	journal	May 2012
Advances in the Determination of Nucleic Acid Conformational Ensembles Salmon, Loïc; Yang, Shan; Al-Hashimi, Hashim M. Annual Review of Physical Chemistry, Vol. 65, Issue 1 https://doi.org/10.1146/annurev-physchem-040412-110059	journal	April 2014
RNA-guided assembly of Rev-RRE nuclear export complexes Bai, Yun; Tambe, Akshay; Zhou, Kaihong eLife, Vol. 3 https://doi.org/10.7554/eLife.03656	journal	August 2014

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