10 The Interactions That Shape RNA Structure

Abstract

This chapter describes the effects of noncovalent interactions on RNA structure and evolution. The building blocks of RNA are well suited for taking advantage of relatively strong noncovalent interactions such as stacking and hydrogen-bonding to form ordered structures. These ordered structures are able to protect RNA from chemical degradation and to allow the specific binding and catalysis required for further evolution.

The noncovalent interactions important for shaping RNA during evolution are revealed by the RNA structures that occur naturally, and by thermodynamic measurements on model systems. First, we discuss the fundamentals of the molecular interactions, then the contributions of stacking, hydrogen-bonding, and metal ions to formation of helices and other motifs. Examples are given of how these interactions shape RNA structures. Finally, some speculations are presented as to how these interactions directed evolution. Since understanding of noncovalent interactions, and knowledge of three-dimensional structures of RNA, are limited, this chapter represents an early stage in the evolution of our understanding of how the two are connected.

FUNDAMENTALS
The equilibrium constant, K, relating the concentrations of two conformations, C₁ and C₂, of an RNA strand is given by(1)K=[C1]/[C2]=exp(-ΔG°/RT)

For an association of two non-self-complementary strands A and B to give A·B, the relevant K = [A·B]/[A][B]. Here ΔG° is the standard free-energy difference between the two conformations, [C₁]/[C₂] and [A·B]/[A][B] are the ratios of the equilibrium concentrations, R is the gas constant (1.987 cal K⁻¹ mole⁻¹), and T is the temperature in Kelvins. Thus, Changes in ΔG° of 1.4 and 2.8...