9ASM

Human Drosha and DGCR8 in complex with Pri-let-7f1

9ASM の概要

• エントリーDOI: 10.2210/pdb9asm/pdb
• EMDBエントリー: 43819
• 分子名称: Isoform 4 of Drosha, Microprocessor complex subunit DGCR8, Pri-let-7f1, ... (6 entities in total)
• 機能のキーワード: rnai, 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: 4
• 化学式量合計: 372068.49

構造登録者

Garg, A.,Joshua-Tor, L. (登録日: 2024-02-26, 公開日: 2024-09-04, 最終更新日: 2024-12-11)

主引用文献

Garg, A.,Shang, R.,Cvetanovic, T.,Lai, E.C.,Joshua-Tor, L.
The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.
Mol.Cell, 84:4175-4190.e6, 2024

PubMed Abstract: MicroRNA (miRNA) biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by the Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryoelectron microscopy (cryo-EM) and biochemical studies of several let-7 family pri-miRNAs in complex with human MP. We show that MP has the structural plasticity to accommodate a range of pri-miRNAs. These structures revealed key features of the 5' UG sequence motif, more comprehensively represented as the "flipped U with paired N" (fUN) motif. Our analysis explains how cleavage of class-II pri-let-7 members harboring a bulged nucleotide generates a non-canonical precursor with a 1-nt 3' overhang. Finally, the MP-SRSF3-pri-let-7f1 structure reveals how SRSF3 contributes to MP fidelity by interacting with the CNNC motif and Drosha's Piwi/Argonaute/Zwille (PAZ)-like domain. Overall, this study sheds light on the mechanisms for flexible recognition, accurate cleavage, and regulated processing of different pri-miRNAs by MP.

PubMed: 39368465
DOI: 10.1016/j.molcel.2024.09.008

実験手法

ELECTRON MICROSCOPY (2.8 Å)