Multilayer checkpoints for microRNA authenticity during RISC assembly

• Published in: EMBO reports Vol. 12; no. 9; pp. 944 - 949
• Main Authors: Kawamata, Tomoko, Yoda, Mayuko, Tomari, Yukihide
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2011; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: 5' Flanking Region; Animals; Argonaute; Argonaute Proteins - metabolism; Authenticity; Base Pairing; Drosophila melanogaster; Embryo, Nonmammalian; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Proteins; Ribonucleic acid; RISC; RNA; RNA, Messenger - metabolism; RNA-Induced Silencing Complex - genetics; RNA-Induced Silencing Complex - metabolism; Scientific Reports
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1038/embor.2011.128

MicroRNAs (miRNAs) function through the RNA‐induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two‐step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5′ phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5′ nucleotide of the miRNA strand and the base‐pairing status in the seed region and the middle of the 3′ region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly. MicroRNAs are loaded into the RISC complex in order to exert their gene‐silencing activity. The authors show that microRNA authenticity is checked at multiple steps during RISC assembly.