Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Abstract

The rapid development of our understanding of the diverse biological roles fulfilled by non-coding RNA has motivated interest in the basic macromolecular behavior, structure, and function of RNA. We focus on two areas in the behavior of complex RNAs. First, we present advances in the understanding of how RNA folding is accomplished in vivo by presenting a mechanism for the action of DEAD-box proteins. Members of this family are intimately associated with almost all cellular processes involving RNA, mediating RNA structural rearrangements and chaperoning their folding. Next, we focus on advances in understanding, and characterizing the basic biophysical forces that govern the folding of complex RNAs. Ultimately we expect that a confluence and synergy between these approaches will lead to profound understanding of RNA and its biology.

Figure 1

Model for general ATP-driven chaperone activity by CYT-19 and other DEAD-box proteins. CYT-19 first binds to structured RNAs using a binding site (RBD). Binding of CYT-19 then allows for structural rearrangement through local, nonprocessive unwinding of helical elements such as the P1 duplex (green and red strands). In general, the accessibility of the targeted structural element determines CYT-19’s unwinding efficiency. Reprinted from [36]. Copyright © 1993–2008 by The National Academy of Sciences of the United States of America, all rights reserved.

Figure 2

A schematic of the hierarchy of forces that determine RNA folding. Electrostatic repulsion between helices (depicted as cylinders) dictates the energetic cost of forming a compact structure. Electrostatic screening from an associated ion atmosphere (blue dots) mitigates this cost (A). Junctions that join helical regions bias the relative positions of the helices that they join, bringing different regions of secondary structure in close proximity (B). Recurring tertiary motifs bind secondary structure elements together and stabilize the final folded state. Some motifs, such as the tetraloop/tetraloop receptor (whose secondary structure is pictured) are highly conserved and ubiquitous throughout RNA structure (C).