第1291回生物科学セミナー
Studies and applications of Argonaute protein
中西 孝太郎 先生（オハイオ州立大学, Assistant Professor, Chemistry & Biochemistry）
2019年07月16日(火) 15:00-16:00 理学部1号館東棟 380号室
MicroRNAs are noncoding RNAs that regulate gene expression in eukaryotes. They are loaded into Argonaute proteins (AGOs) to form RNA-induced silencing complexes (RISCs). Of the four human AGO paralogs, only AGO2 has been shown to have slicer activity. This talk will describe our recent discovery that specific microRNAs catalytically activate AGO3. Our crystal structure of AGO3 in complex with guide RNA shows the nucleic acid-binding channel with its unique shape, suggesting a different activation mechanism. I will also report our 1.9 Å crystal structure of guide-bound AGO4 with 17 water molecules forming two clusters in the protein interior. The cluster formation essential for the RISC assembly is typical of AGOs but not of PIWI proteins. Lastly, I will introduce our AGO-based programmable RNA restriction enzyme that cleaves a 5’ untranslated region of HIV-1 at desired positions.
