Section 23.2.4.6. Single-stranded sequence-nonspecific RNA–protein interactions

There is a single example of a single-stranded RNA–protein complex which is sequence-nonspecific. The structure of the vaccinia RNA methyltransferase VP39 bound to a 5′m⁷G-capped RNA hexamer reveals a mechanism of nonspecific recognition reminiscent of the Klenow fragment–DNA tetramer complex (Hodel et al., 1998). The RNA forms two short single-stranded helices of three bases each. The first of these helices binds in the active site of VP39 solely through hydrogen bonds between the protein and the ribose–phosphate backbone. The bases of the RNA strand stack together as trimers, but do not form any interactions with the protein (Fig. 23.2.4.4). Like the Klenow–DNA complex, this observation suggests an intuitive mechanism for sequence-nonspecific nucleic acid binding, where the single-stranded RNA forms short transient helices driven by intramolecular stacking interactions. The protein then recognizes and stabilizes the helical backbone conformation formed by this transient stacking without interacting with the bases themselves.

Figure 23.2.4.4| top | pdf | The sequence-nonspecific recognition of single-stranded nucleic acid. (a) Oligo(dT) bound in the exonuclease active site of DNA polymerase I Klenow fragment (Freemont et al., 1988). (b) A short capped RNA transcript bound to the VP39 RNA methyltransferase (Hodel et al., 1998). Both proteins primarily interact with the backbone of the nucleic acid.