Bulges are an important structural motif in RNA and can be used as recognition and interaction sites in RNA-protein interaction and RNA-RNA interaction. Here we report the first crystal structure of a bulged RNA tetraplex at 1.1 Å resolution. The hexamer r(U)(BrdG)r(UGGU) forms a parallel tetraplex with the uridine sandwiched by guanines bulging out. The bulged uridine adopts the syn glycosidic conformation and its O2 and N3 atoms face outwards, serving as an effective recognition and interaction site. The bulge formation both widens the groove width and changes the groove hydrogen-bonding pattern on its 5′ side. However, the bulge does not make any bends or kinks in the tetraplex structure. The present study demonstrates the dramatic difference between uridine and guanine in forming tetraplex structure. In addition, both G(syn) tetrad and G(anti) tetrad have been observed. They display the same base-pairing pattern and similar C1′-C1′ distance but different hydrogen-bonding patterns in the groove.
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We acknowledge the support of this work by the National Institutes of Health grant GM-17378 and the Board of Regents of Ohio for an Ohio Eminent Scholar Chair and Endowment to M.S. We also thank the use of the Advanced Photon Source supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-Eng-38.