LidNA, a miRNA inhibitor constructed with unmodified DNA, requires an xxxA insertion sequence in miRNA binding site for its potent inhibitory activity

FEBS Letters

article

Akira Tachibana¹  Satoshi Saito¹  Yukiko Fujiyama¹  Toshizumi Tanabe¹ 

[1] Department of Bioengineering, Graduate School of Engineering, Osaka City University

关键词: argonaute;    G-quartet structure;    LidNA;    miRNA;    miRNA inhibitor;    RISC;   

DOI  :  10.1002/1873-3468.13756

来源: John Wiley & Sons Ltd.

【 摘 要 】

The involvement of miRNAs in the pathogenesis of various diseases, including cancer, poses the need for developing miRNA inhibitors. Previously, using unmodified DNA, we designed LidNA, which inhibited miRNA function more potently than 20 -O-methylated RNA and locked nucleic acid. LidNA consists of a complementary sequence to miRNA flanked by two structured DNAs. Alterations in the connected sequences between the complementary region and structured region modestly affect miRNA inhibition activity. Surprisingly, variations in the mismatched insertion sequence in the center of the complementary sequence significantly affect activity. The central insertion sequence xxxA is required for the potent miRNA inhibitory effects of LidNA. This suggests that both the structure and insertion sequence of LidNA and other miRNA inhibitors should be considered for maximal miRNA inhibitory activity.

【 授权许可】

Unknown