6NIT

Human Argonaute2-miR-122 bound to a target RNA with four central mismatches (bu4)

6NIT の概要

• エントリーDOI: 10.2210/pdb6nit/pdb
• 分子名称: Protein argonaute-2, RNA (5'-R(P*UP*GP*GP*AP*GP*UP*GP*UP*GP*AP*CP*AP*AP*UP*GP*GP*UP*GP*UP*UP*U)-3'), RNA (5'-R(P*AP*AP*CP*AP*CP*CP*AP*UP*CP*CP*AP*AP*CP*AP*CP*UP*CP*CP*AP*AP*A)-3') (3 entities in total)
• 機能のキーワード: rna-binding protein, microrna, target directed microrna decay, hydrolase, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 222853.38

構造登録者

Sheu-Gruttadauria, J.,MacRae, I.J. (登録日: 2018-12-31, 公開日: 2019-08-07, 最終更新日: 2024-03-13)

主引用文献

Sheu-Gruttadauria, J.,Pawlica, P.,Klum, S.M.,Wang, S.,Yario, T.A.,Schirle Oakdale, N.T.,Steitz, J.A.,MacRae, I.J.
Structural Basis for Target-Directed MicroRNA Degradation.
Mol.Cell, 75:1243-1255.e7, 2019

PubMed Abstract: MicroRNAs (miRNAs) broadly regulate gene expression through association with Argonaute (Ago), which also protects miRNAs from degradation. However, miRNA stability is known to vary and is regulated by poorly understood mechanisms. A major emerging process, termed target-directed miRNA degradation (TDMD), employs specialized target RNAs to selectively bind to miRNAs and induce their decay. Here, we report structures of human Ago2 (hAgo2) bound to miRNAs and TDMD-inducing targets. miRNA and target form a bipartite duplex with an unpaired flexible linker. hAgo2 cannot physically accommodate the RNA, causing the duplex to bend at the linker and display the miRNA 3' end for enzymatic attack. Altering 3' end display by changing linker flexibility, changing 3' end complementarity, or mutationally inducing 3' end release impacts TDMD efficiency, leading to production of distinct 3'-miRNA isoforms in cells. Our results uncover the mechanism driving TDMD and reveal 3' end display as a key determinant regulating miRNA activity via 3' remodeling and/or degradation.

PubMed: 31353209
DOI: 10.1016/j.molcel.2019.06.019

実験手法

X-RAY DIFFRACTION (3.8 Å)