9ASQ

Human Drosha, DGCR8 and SRSF3 in complex with Pri-let-7f1

Summary for 9ASQ

• Entry DOI: 10.2210/pdb9asq/pdb
• EMDB information: 43823
• Descriptor: Isoform 4 of Drosha, Microprocessor complex subunit DGCR8, Pri-let-7f1, ... (7 entities in total)
• Functional Keywords: rnai, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 391445.27

Authors

Garg, A.,Joshua-Tor, L. (deposition date: 2024-02-26, release date: 2024-09-04, Last modification date: 2024-12-11)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3 Å)