Principles and Properties of RNA Self-Assembly

Undergraduate Honors Thesis

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/zw12z5930

Abstract

Ribonucleoprotein (RNP) granules are membraneless assemblies of condensed RNA and protein that form through multivalent interactions between the constituent components. Recently, RNA self-assembly has been shown to contribute to the formation of stress granules, which are RNP granules associated with the stress response and neurodegeneration. However, little is understood about the properties of self-assembled RNA. Here, I show that different RNA sequences can self- assemble into condensates with distinct material properties and partitioning preferences in vitro. Due to interactions that minimize surface free energy, RNA self-assembly can generate the spontaneous self-patterning of RNA assemblies. By reducing surface free energy, thereby promoting RNA-RNA interactions, RNAs stabilize multiphase RNA assemblies or assemble into surface shells composed of a hyperstable interacting meshwork of RNA. In principle, the thermostability of RNA self-assembly could give rise to uncontrolled RNA aggregation in the cell without modulatory mechanisms, and I show that the condensation of certain transcripts onto stress granules can be limited by the DEAD-box helicase eIF4A and potentially other helicases. These data suggest a view of the cell where intermolecular RNA-RNA interactions drive RNA self-assembly and where the cell utilizes a diversity of mechanisms to limit such RNA based condensation.

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