Details

Autor(en) / Beteiligte

• Sheng, Jia
• Larsen, Aaron
• Heuberger, Benjamin D
• Blain, J. Craig
• Szostak, Jack W

Titel

Crystal Structure Studies of RNA Duplexes Containing s2U:A and s2U:U Base Pairs

Ist Teil von

• Journal of the American Chemical Society, 2014-09, Vol.136 (39), p.13916-13924

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2014

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 (s2U) is a modified nucleobase found in certain tRNAs. Thermodynamic studies have evaluated the effects of s2U 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 s2U-containing RNA duplexes have yet been reported. We present here two high-resolution crystal structures of heptamer RNA duplexes (5′-uagc s 2 U cc-3′ paired with 3′-aucg A gg-5′ and with 3′-aucg U gg-5′) containing s2U:A and s2U: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 s2U: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 s2U: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.