Unlike DNA, in addition to the 20 -OH group, uracil nucleobase and its modifications play essential roles in structure and function diversities of non- coding RNAs. Non-canonical U.U base pair is ubiquitous in non-coding RNAs, which are highly diversified. However, it is not completely clear how uracil plays the diversifing roles. To investigate and compare the uracil in U-A and U.U base pairs, we have decided to probe them with a selenium atom by synthesizing the novel 4-Se-uridine (SeU) phosphoramidite and Se-nucleobase-modified RNAs (SeU-RNAs), where the exo-4-oxygen of uracil is replaced by selenium. Our crystal structure studies of U-A and U.U pairs reveal that the native and Se-derivatized structures are virtually identical, and both U-A and U.U pairs can accommodate large Se atoms. Our thermostability and crystal structure studies indicate that the weakened H-bonding in U-A pair may be compensated by the base stacking, and that the stacking of the trans- Hoogsteen U.U pairs may stabilize RNA duplex and its junction. Our result confirms that the hydrogen bond (O4.. .H-C5) of the Hoogsteen pair is weak. Using the Se atom probe, our Se- functionalization studies reveal more insights into the U.U interaction and U-participation in structure and function diversification of nucleic acids.
Structural insights of non-canonical U•U pair and Hoogsteen interaction probed with Se atom Nucl. Acids Res. (2013) 41 (22): 10476-10487 first published online September 5, 2013 doi:10.1093/nar/gkt799
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