Investigation of the interactions in RNA recognition motif-RNA complexes: small molecule inhibitors and kinetics of dissociation

Baek, Jung-Un

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https://hdl.handle.net/2142/34369 Copy

Description

Title

Investigation of the interactions in RNA recognition motif-RNA complexes: small molecule inhibitors and kinetics of dissociation

Author(s)

Baek, Jung-Un

Issue Date

2012-09-18T21:13:39Z

Director of Research (if dissertation) or Advisor (if thesis)

Baranger, Anne M.

Doctoral Committee Chair(s)

Baranger, Anne M.

Committee Member(s)

• Katzenellenbogen, John A.
• Hergenrother, Paul J.
• Zhao, Huimin

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• RNA binding protein
• Small molecule
• RNA recognition motif
• Kinetics
• Protein-RNA interaction

Abstract

The RNA recognition motif (RRM) is the most abundant RNA binding domain that is found in all organisms. RRM-containing proteins participate in most steps of gene expression, including translation, splicing, modification and transport of RNA. This dissertation aims to help understand the interactions of the RNA recognition motif and RNA by developing a small molecule modulator of the interaction and analyzing the kinetics of dissociation. The first chapter gives an introduction to the function and structural characteristics of RNA binding proteins, RNA recognition motifs and two RRM proteins, U1A and Sex lethal protein. Chapter 2 describes the identification and analysis of three small molecules that disrupt two different RRM-RNA complexes, Sex lethal protein-tra RNA and U1A-SL2 RNA. The research discussed in chapter 3 focus on the role of positively charged residues in the U1A protein and SL2 RNA complex dissociation process. Analysis of kinetics data obtained by temperature jump and stopped-flow experiments showed that the location of the electrostatic interaction controls the rate of different steps in the complex dissociation pathway. Chapter 4 is a description of a simple and rapid method to detect RNA splice variants using biarsenical dyes and split tetracysteine moieties, which may accelerate biochemical studies of alternative splicing and identification of factors that modulate RNA splicing.

Graduation Semester

2012-08

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http://hdl.handle.net/2142/34369

Copyright and License Information

Copyright 2012 Jung-Un Baek

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