ArticleNature structural & molecular biology2013
Biased Brownian ratcheting leads to pre-mRNA remodeling and capture prior to first-step splicing.
Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 67 citations in OpenAlex.
- Exchange dynamics and kinetic control of gene regulation complexes.Nature reviews. Molecular cell biology · 2026Review
- G-patch proteins: important regulators of pre-mRNA splicing and ribosome biogenesis.Frontiers in cell and developmental biology · 2026Review
- Split-APEX implicates splicing factor SRSF1 and splicing helicases in ribosomal biogenesis.Frontiers in molecular biosciences · 2025Article
- Base-Stacking Heterogeneity in RNA Resolved by Fluorescence-Detected Circular Dichroism Spectroscopy.The journal of physical chemistry letters · 2022Article
- Measuring the impact of cofactors on RNA helicase activities.Methods (San Diego, Calif.) · 2022Article
- Bayesian machine learning analysis of single-molecule fluorescence colocalization images.eLife · 2022Article
- Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment.Cell death & disease · 2021Review
- The structure of Prp2 bound to RNA and ADP-BeFActa crystallographica. Section D, Structural biology · 2021Article
- Structural basis for conformational equilibrium of the catalytic spliceosome.Molecular cell · 2021Article
- Cooperative Analysis of Structural Dynamics in RNA-Protein Complexes by Single-Molecule Förster Resonance Energy Transfer Spectroscopy.Molecules (Basel, Switzerland) · 2020Review
- Structural and functional modularity of the U2 snRNP in pre-mRNA splicing.Critical reviews in biochemistry and molecular biology · 2019Review
- Biological Pathway Specificity in the Cell-Does Molecular Diversity Matter?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Coming Together: RNAs and Proteins Assemble under the Single-Molecule Fluorescence Microscope.Cold Spring Harbor perspectives in biology · 2019Review
- Analysis of spliceosome dynamics by maximum likelihood fitting of dwell time distributions.Methods (San Diego, Calif.) · 2019Article
- Crystal structure of the spliceosomal DEAH-box ATPase Prp2.Acta crystallographica. Section D, Structural biology · 2018Article
- Hierarchical mechanism of amino acid sensing by the T-box riboswitch.Nature communications · 2018Article
- Life under the Microscope: Single-Molecule Fluorescence Highlights the RNA World.Chemical reviews · 2018Review
- Soft Interactions with Model Crowders and Non-canonical Interactions with Cellular Proteins Stabilize RNA Folding.Journal of molecular biology · 2018Article
- Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine.Nature structural & molecular biology · 2017Review
- Methodologies for studying the spliceosome's RNA dynamics with single-molecule FRET.Methods (San Diego, Calif.) · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The spliceosome is a dynamic ribonucleoprotein (RNP) machine that catalyzes the removal of introns during the two transesterification steps of eukaryotic pre-mRNA splicing. Here we used single-molecule fluorescence resonance energy transfer to monitor the distance of the 5' splice site (5' SS) and branch point (BP) of pre-mRNA in affinity-purified spliceosomes stalled by a mutation in the DExD/H-box helicase Prp2 immediately before the first splicing step. Addition of recombinant Prp2 together with NTP and protein cofactor Spp2 rearranges the spliceosome-substrate complex to reversibly explore conformations with proximal 5' SS and BP that accommodate chemistry. Addition of Cwc25, a small heat-stable splicing factor, then strongly biases this equilibrium toward the proximal conformation, promoting efficient first-step splicing. The spliceosome thus functions as a biased Brownian ratchet machine where a helicase unlocks thermal fluctuations subsequently rectified by a cofactor 'pawl', a principle possibly widespread among the many helicase-driven RNPs.
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Registered trials
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.