Evidence map›Paper›PMID 39368465›Full record

ArticleMolecular cell2024

The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.

Ankur Garg, Renfu Shang, Todor Cvetanovic, Eric C Lai, Leemor Joshua-Tor

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

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  15. The biogenesis and regulation of animal microRNAs.Nature reviews. Molecular cell biology · 2025
    Review
  16. Review
  17. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Ankur GargW. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Renfu ShangDevelopmental Biology Program, Sloan Kettering Institute, 430 East 67th St, ROC-10, New York, NY 10065, USA.
Todor CvetanovicW. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Eric C LaiDevelopmental Biology Program, Sloan Kettering Institute, 430 East 67th St, ROC-10, New York, NY 10065, USA.
Leemor Joshua-TorW. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA; Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: leemor@cshl.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI David A Tuveson · 1987 to 2026
$118.9M
Selective regulatory and biogenesis mechanisms for microRNAsR01GM083300 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Eric C Lai · 2007 to 2026
$9.8M
The let-7 Regulatory NetworkR01GM114147 · NIGMS · COLD SPRING HARBOR LABORATORY · PI JOSHUA-TOR, LEEMOR · 2016 to 2019
$1.4M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA045508NIGMS NIH HHS R01 GM083300NIGMS NIH HHS R01 GM114147
6 · The paper itself

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.

Indexed as

Cryoelectron MicroscopyMicroRNAsRibonuclease IIIRNA-Binding ProteinsRNA Processing, Post-TranscriptionalHEK293 CellsHumansNucleic Acid ConformationProtein BindingDGCR8 protein, humanDROSHA protein, humanMicroRNAsmirnlet7 microRNA, humanRibonuclease IIIRNA-Binding Proteinscryo-EMlet-7 miRNAMicroprocessormiRNA biogenesisprotein-RNARNAi

Identifiers

PMID39368465
PMCPMC11560618

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.