Structural insights of non-canonical U*U pair and Hoogsteen interaction probed with Se atom.

摘要

Unlike DNA, in addition to the 2'-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 ((Se)U) phosphoramidite and Se-nucleobase-modified RNAs ((Se)U-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.Registry Number/Name of Substance 0 (Organophosphorus Compounds). 0 (RNA, Untranslated). 0 (phosphoramidite). 56HH86ZVCT (Uracil). H6241UJ22B (Selenium). WHI7HQ7H85 (Uridine).