The multiple flavors of GoU pairs in RNA

Abstract

Wobble GU pairs (or GoU) occur frequently within double-stranded RNA helices interspersed within the standard G═C and A─U Watson-Crick pairs. However, other types of GoU pairs interacting on their Watson-Crick edges have been observed. The structural and functional roles of such alternative GoU pairs are surprisingly diverse and reflect the various pairings G and U can form by exploiting all the subtleties of their electronic configurations. Here, the structural characteristics of the GoU pairs are updated following the recent crystallographic structures of functional ribosomal complexes and the development in our understanding of ribosomal translation.

Keywords: GoU pair; anticodon; codon; mRNA; miscoding; ribosome; tRNA; tautomer.

Figure 1

In the usual GoU wobble pair, the uracil base is displaced in the deep major groove region of a RNA double helix. In the figure, GoU and UoG pairs are compared. If one slides the C1′ atom of the G in a GoU pair on the C1′ atom of the U of a UoG pair, there is a displacement around 2 Å between the C1′ atoms of the paired base. Unlike the complementary Watson‐Crick base pairs (A─U, G═C), the GoU base pairs are not isosteric. Geometrically, isostericity between base pairs means that the positions and distances between the C1′ carbon atoms are very similar72

Figure 2

A wobble GoU pair (from PDB 4PCO73) with a water molecule in the minor groove (green cross) and a hydrated ion (here a cobalt hexamine) in the major groove. A water molecule linking a phosphate oxygen, the N7(G), and an ammine group is also shown. All distances are in angstrom and between the heavy atoms, except for the two base‐base H bonds

Figure 3

At the top, a usual GoU pair is represented and below a bifurcated GoU pair in which the O4(U) points towards the N1(G) and the N2(G) simultaneously. Such base pairs have not been found isolated and embedded within a helix, but only together with other non‐Watson‐Crick pairs. More on bifurcated base GoU pairs can be found in Leontis et al26

Figure 4

Two theoretical forms of tautomeric GoU pairs. At the top, the G adopts the enol form (and not the usual keto form), at the bottom, the U adopts the enol form (and the usual keto form). Crystallography cannot distinguish between these two possibilities. Physically, the two states are equivalent with the protons oscillating between the O6 and O4 oxygen atoms and between the N1 and N3 nitrogen atoms. Such tautomeric GoU pairs are isosteric between themselves like Watson‐Crick G═C pairs. Such tautomeric base pairs are undistinguishable from G═C pairs through interactions in the minor groove side.30 Such tautomeric Watson‐Crick–like pairs have been observed by crystallography with natural bases33, 36, 38, 39 or modified Uridines52, 53

Figure 5

At the top is shown the usual GoU pair with the displacement of the U in the major groove, and below is shown the novel GoU pair with the U displaced into the minor groove. In the latter case, the electronic structure of the U could not be determined by X‐ray crystallography, but the shape of the base pair was clearly indicated by the electron density.35 In the drawing, we follow the choice made by Sochacka et al58 where the negative charged is shown delocalized. In the crystal structure,35 X = S and R = methylaminomethyl

Figure 6

The three flavors of GoU pairs discussed: At the top, the usual mode, the GoU wobble has the U displaced into the major groove; below (thick dark lines), the anionic mode, the GoU pair has the U (that must be modified) displaced into the minor groove, and at the right, the tautomeric mode, the GoU pair is isosteric to a G═C pair