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Crystal Structure Studies of RNA Duplexes Containing s<sup>2</sup>U:A and s<sup>2</sup>U:U Base Pairs
Structural studies of modified nucleobases
in RNA duplexes are
critical for developing a full understanding of the stability and
specificity of RNA base pairing. 2-Thio-uridine (s<sup>2</sup>U) is
a modified nucleobase found in certain tRNAs. Thermodynamic studies
have evaluated the effects of s<sup>2</sup>U on base pairing in RNA,
where it has been shown to stabilize U:A pairs and destabilize U:G
wobble pairs. Surprisingly, no high-resolution crystal structures
of s<sup>2</sup>U-containing RNA duplexes have yet been reported.
We present here two high-resolution crystal structures of heptamer
RNA duplexes (5′-uagc<b><u>s</u></b><sup><b><u>2</u></b></sup><b><u>U</u></b>cc-3′ paired with 3′-aucg<b><u>A</u></b>gg-5′ and with 3′-aucg<b><u>U</u></b>gg-5′) containing s<sup>2</sup>U:A and s<sup>2</sup>U:U pairs, respectively. For comparison, we also present the structures
of their native counterparts solved under identical conditions. We
found that replacing O2 with S2 stabilizes the U:A base pair without
any detectable structural perturbation. In contrast, an s<sup>2</sup>U:U base pair is strongly stabilized in one specific U:U pairing
conformation out of four observed for the native U:U base pair. This
s<sup>2</sup>U:U stabilization appears to be due at least in part
to an unexpected sulfur-mediated hydrogen bond. This work provides
additional insights into the effects of 2-thio-uridine on RNA base
pairing