Asymmetry in RNA pseudoknots: observation and theory

Abstract

RNA can fold into a topological structure called a pseudoknot, composed of non-nested double-stranded stems connected by single-stranded loops. Our examination of the PseudoBase database of pseudoknotted RNA structures reveals asymmetries in the stem and loop lengths and provocative composition differences between the loops. By taking into account differences between major and minor grooves of the RNA double helix, we explain much of the asymmetry with a simple polymer physics model and statistical mechanical theory, with only one adjustable parameter.

Figure 1

(a) An ABAB-pseudoknot is depicted in planar representation. The structure is composed of two double-helical stems (with s₁ and s₂ base pairs) and the three single-stranded loops of lengths L₁, L₂ and L₃ nucleotides. (b) The 3D fold of the same knot is depicted. The x, y, z axes point left, out, up. Coaxial stacking interactions between stems 1 and 2 can stabilize the structure, particularly if L₂ = 0. Note that loop 1 lies on the major groove side, while loop 3 lies on the minor groove side.

Figure 2

The statistics of ABAB-pseudoknots in PseudoBase (obs) with L₂ = 0 is compared with our theory (thy). (a) Stems favor different numbers of base pairs s₁ and s₂. (b) Loop lengths L₁ and L₃ are also asymmetric.

Figure 3

The distances $D_{L_1}$ and $D_{L_3}$ across the major or minor groove as a function of the number of bases s in the associated stem. The differences are due to the geometries of major- and minor grooves.