RNA structure prediction using high-throughput chemical modification techniques Public Deposited

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  • March 19, 2019
Creator
  • Lavender, Christopher Andrew
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Functional RNA molecules require the formation of defined structures in order to perform their critical tasks in biology. Complete understanding of this structure-function relationship in RNA requires the elucidation of accurate RNA structural models. RNA chemical modification has proven to be an invaluable tool in the characterization of RNA structure. Recently, the throughput of RNA chemical modification approaches has increased significantly through the adaptation of chemical modification techniques to next-generation sequencing platforms. In this work, I create several new methodologies for the generation of accurate RNA structural models based on high-throughput RNA chemical modification analysis. First, I create a general methodology for predicting three-dimensional RNA structures based on RNA interactions implicated by biochemical and bioinformatic approaches. In this work, I develop a three-dimensional model for the hepatitis C virus internal ribosome entry site (HCV IRES) pseudoknot domain. This methodology is then applied to a new high-throughput chemical modification approach called RING-MaP (RNA interaction groups identified by mutational profiling). Implicated interactions from RING-MaP analysis allow for accurate prediction of RNA tertiary folds. Second, I create an algorithm for the comparison of high-throughput chemical modification data from related RNA sequences. Using SHAPE chemical modification alone, this approach allows recapitulation of ribosomal RNA alignments made using sequence identity. Chemical modification data for three HIV-related viral RNA genomes are then compared. Following creation of chemical modification-dependent alignments, statistically related RNA structures are found across the three viral genomes. Consensus secondary structures considering both chemical modification data and covariation are then made, recapitulating all known RNA structures in the HIV genome and suggesting previously undescribed functional elements.
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  • In Copyright
Advisor
  • Weeks, Kevin
Degree
  • Doctor of Philosophy
Graduation year
  • 2014
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