Evidence map›Paper›PMID 31640290›Full record

ArticleBiomolecules2019

Disclosing the Impact of Carcinogenic SF3b Mutations on Pre-mRNA Recognition Via All-Atom Simulations.

Jure Borišek, Andrea Saltalamacchia, Anna Gallì, Giulia Palermo, Elisabetta Molteni, Luca Malcovati, Alessandra Magistrato

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
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

12 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Exploring Disordered Regions of Human Spliceosome Proteins.The journal of physical chemistry letters · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Structural studies of the spliceosome: Bridging the gaps.Current opinion in structural biology · 2022
    Review
  7. Intrinsically disordered ectodomain modulates ion permeation through a metal transporter.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. Mechanism of RNA recognition by a Musashi RNA-binding protein.Current research in structural biology · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Jure BorišekCNR-IOM-Democritos National Simulation Center c/o SISSA, 34136 Trieste, Italy. jure.borisek@ki.si.
Andrea SaltalamacchiaInternational School for Advanced Studies (SISSA), 34136 Trieste, Italy. asaltala@sissa.it.
Anna GallìDepartment of Hematology, IRCCS S. Matteo Hospital Foundation, 27100 Pavia, Italy. anna.galli@unipv.it.
Giulia PalermoDepartment of Bioengineering, University of California Riverside, Riverside CA 92521, USA. gpalermo@engr.ucr.edu.
Elisabetta MolteniDepartment of Molecular Medicine, University of Pavia, 27100 Pavia, Italy. elisabetta.molteni@unipv.it.
Luca MalcovatiDepartment of Hematology, IRCCS S. Matteo Hospital Foundation, 27100 Pavia, Italy. luca.malcovati@unipv.it.
Alessandra MagistratoCNR-IOM-Democritos National Simulation Center c/o SISSA, 34136 Trieste, Italy. alessandra.magistrato@sissa.it.
Scuola Internazionale Superiore di Studi Avanzati · ITUniversity of Pavia · ITUniversity of California, Riverside · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The spliceosome accurately promotes precursor messenger-RNA splicing by recognizing specific noncoding intronic tracts including the branch point sequence (BPS) and the 3'-splice-site (3'SS). Mutations of Hsh155 (yeast)/SF3B1 (human), which is a protein of the SF3b factor involved in BPS recognition and induces altered BPS binding and 3'SS selection, lead to mis-spliced mRNA transcripts. Although these mutations recur in hematologic malignancies, the mechanism by which they change gene expression remains unclear. In this study, multi-microsecond-long molecular-dynamics simulations of eighth distinct ∼700,000 atom models of the spliceosome Bact complex, and gene sequencing of SF3B1, disclose that these carcinogenic isoforms destabilize intron binding and/or affect the functional dynamics of Hsh155/SF3B1 only when binding non-consensus BPSs, as opposed to the non-pathogenic variants newly annotated here. This pinpoints a cross-talk between the distal Hsh155 mutation and BPS recognition sites. Our outcomes unprecedentedly contribute to elucidating the principles of pre-mRNA recognition, which provides critical insights on the mechanism underlying constitutive/alternative/aberrant splicing.

Indexed as

Molecular Dynamics SimulationMutationCarcinogensHumansPhosphoproteinsPrincipal Component AnalysisRibonucleoprotein, U2 Small NuclearRNA PrecursorsRNA SplicingRNA Splicing FactorsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsStatic ElectricityCarcinogensHSH155 protein, S cerevisiaePhosphoproteinsRibonucleoprotein, U2 Small NuclearRNA PrecursorsRNA Splicing FactorsSaccharomyces cerevisiae ProteinsSF3B1 protein, humanmolecular dynamicsRNAspliceosomesplicing

Identifiers

PMID31640290
PMCPMC6843770
OpenAlexW2980397543

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.