Investigation of SHAPE mechanism with RNA 3D structure modeling

ORAL

Abstract

Selective 2$'$-hydroxyl acylation by primer extension (SHAPE) chemical probing method for RNA reflects local structural dynamics, which is intrinsically related to RNA three-dimensional structure. To gain quantitative insights into the relationship between RNA three-dimensional structure and SHAPE reactivity, we develop an algorithm to rebuild the SHAPE profile from the three-dimensional structure. The algorithm starts from RNA structures and combines nucleotide interaction strength and conformational flexibility, ligand (SHAPE reagent) accessibility and base-pairing pattern through a composite function. Comparisons between the predicted SHAPE profile and experimental SHAPE data show high correlation, suggesting the validity of the extracted analytical function. The validity of the theory supports the model for the key factors that determine SHAPE reactivity profile. Furthermore, the theory offers an effective method to select viable RNA three-dimensional structures from an ensemble of decoy structure models.

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Authors

  • Peinan Zhao

    Department of Physics and Department of Biochemistry, University of Missouri, Columbia, MO 65211

  • Mark Neubauer

    University of Missouri-Columbia, Southern Illinois University Carbondale, Indiana University, Purdue University, Argonne National Laboratory, University of Missouri, College of Physics Science, Qingda University, Qingdao, 266071, China, Indian Institute of Science, Bangalore, India, University of Massachusetts Amherst, Iowa State University, Technical University of Denmark, University of Missouri - Columbia, University of California - San Diego, La Jolla, CA 92093, Department of Physics, University of Missouri-Columbia, Columbia, Missouri 65211, Department of Physics and Astronomy, University of Missouri-Columbia, University of Missouri, Columbia, MO, Department of Physics and Department of Biochemistry, University of Missouri, Columbia, MO 65211, Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, Univ of Missouri - Columbia, Duke University, Shanghai Jiaotong University, Ames Laboratory, U.S. DOE, Texas Center of Superconductivity and the Department of Physics, University of Houston, Institute of Physics, Siberian Division, Russian Academy of Sciences, Krasnoyarsk, 66036, Russia, Oak Ridge National Laboratory, NIST Center for Neutron Research, MU Research Reactor, Ames Laboratory and Dep. of Physics and Astronomy, Iowa State University, AmesAmes Laboratory and Dep. of Physics and Astronomy, Iowa State University, HFIR, Oak Ridge National Laboratory, University of Illinois at Urbana-Champaign

  • Mark Neubauer

    University of Missouri-Columbia, Southern Illinois University Carbondale, Indiana University, Purdue University, Argonne National Laboratory, University of Missouri, College of Physics Science, Qingda University, Qingdao, 266071, China, Indian Institute of Science, Bangalore, India, University of Massachusetts Amherst, Iowa State University, Technical University of Denmark, University of Missouri - Columbia, University of California - San Diego, La Jolla, CA 92093, Department of Physics, University of Missouri-Columbia, Columbia, Missouri 65211, Department of Physics and Astronomy, University of Missouri-Columbia, University of Missouri, Columbia, MO, Department of Physics and Department of Biochemistry, University of Missouri, Columbia, MO 65211, Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, Univ of Missouri - Columbia, Duke University, Shanghai Jiaotong University, Ames Laboratory, U.S. DOE, Texas Center of Superconductivity and the Department of Physics, University of Houston, Institute of Physics, Siberian Division, Russian Academy of Sciences, Krasnoyarsk, 66036, Russia, Oak Ridge National Laboratory, NIST Center for Neutron Research, MU Research Reactor, Ames Laboratory and Dep. of Physics and Astronomy, Iowa State University, AmesAmes Laboratory and Dep. of Physics and Astronomy, Iowa State University, HFIR, Oak Ridge National Laboratory, University of Illinois at Urbana-Champaign

  • Mark Neubauer

    University of Missouri-Columbia, Southern Illinois University Carbondale, Indiana University, Purdue University, Argonne National Laboratory, University of Missouri, College of Physics Science, Qingda University, Qingdao, 266071, China, Indian Institute of Science, Bangalore, India, University of Massachusetts Amherst, Iowa State University, Technical University of Denmark, University of Missouri - Columbia, University of California - San Diego, La Jolla, CA 92093, Department of Physics, University of Missouri-Columbia, Columbia, Missouri 65211, Department of Physics and Astronomy, University of Missouri-Columbia, University of Missouri, Columbia, MO, Department of Physics and Department of Biochemistry, University of Missouri, Columbia, MO 65211, Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, Univ of Missouri - Columbia, Duke University, Shanghai Jiaotong University, Ames Laboratory, U.S. DOE, Texas Center of Superconductivity and the Department of Physics, University of Houston, Institute of Physics, Siberian Division, Russian Academy of Sciences, Krasnoyarsk, 66036, Russia, Oak Ridge National Laboratory, NIST Center for Neutron Research, MU Research Reactor, Ames Laboratory and Dep. of Physics and Astronomy, Iowa State University, AmesAmes Laboratory and Dep. of Physics and Astronomy, Iowa State University, HFIR, Oak Ridge National Laboratory, University of Illinois at Urbana-Champaign

  • Mark Neubauer

    University of Missouri-Columbia, Southern Illinois University Carbondale, Indiana University, Purdue University, Argonne National Laboratory, University of Missouri, College of Physics Science, Qingda University, Qingdao, 266071, China, Indian Institute of Science, Bangalore, India, University of Massachusetts Amherst, Iowa State University, Technical University of Denmark, University of Missouri - Columbia, University of California - San Diego, La Jolla, CA 92093, Department of Physics, University of Missouri-Columbia, Columbia, Missouri 65211, Department of Physics and Astronomy, University of Missouri-Columbia, University of Missouri, Columbia, MO, Department of Physics and Department of Biochemistry, University of Missouri, Columbia, MO 65211, Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, Univ of Missouri - Columbia, Duke University, Shanghai Jiaotong University, Ames Laboratory, U.S. DOE, Texas Center of Superconductivity and the Department of Physics, University of Houston, Institute of Physics, Siberian Division, Russian Academy of Sciences, Krasnoyarsk, 66036, Russia, Oak Ridge National Laboratory, NIST Center for Neutron Research, MU Research Reactor, Ames Laboratory and Dep. of Physics and Astronomy, Iowa State University, AmesAmes Laboratory and Dep. of Physics and Astronomy, Iowa State University, HFIR, Oak Ridge National Laboratory, University of Illinois at Urbana-Champaign