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

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

Baek, Jung-Un

关键词: RNA binding protein;    Small molecule;    RNA recognition motif;    Kinetics;    Protein-RNA interaction;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/34369/Baek_Jung-Un.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The RNA recognition motif (RRM) is the most abundant RNA binding domain that isfound 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 helpunderstand the interactions of the RNA recognition motif and RNA by developing a smallmolecule modulator of the interaction and analyzing the kinetics of dissociation. The firstchapter gives an introduction to the function and structural characteristics of RNA bindingproteins, RNA recognition motifs and two RRM proteins, U1A and Sex lethal protein. Chapter 2describes the identification and analysis of three small molecules that disrupt two differentRRM-RNA complexes, Sex lethal protein-tra RNA and U1A-SL2 RNA. The research discussedin chapter 3 focus on the role of positively charged residues in the U1A protein and SL2 RNAcomplex dissociation process. Analysis of kinetics data obtained by temperature jump andstopped-flow experiments showed that the location of the electrostatic interaction controls therate of different steps in the complex dissociation pathway. Chapter 4 is a description of asimple and rapid method to detect RNA splice variants using biarsenical dyes and splittetracysteine moieties, which may accelerate biochemical studies of alternative splicing andidentification of factors that modulate RNA splicing.