Evidence map›Paper›PMID 26414013›Full record

ArticleNature methods2015

Single Molecule Cluster Analysis dissects splicing pathway conformational dynamics.

Mario R Blanco, Joshua S Martin, Matthew L Kahlscheuer, Ramya Krishnan, John Abelson, Alain Laederach, Nils G Walter

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

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  10. The roles of structural dynamics in the cellular functions of RNAs.Nature reviews. Molecular cell biology · 2019
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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 4 institutions in 1 country.

Mario R BlancoDepartment of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, Michigan, USA.
Joshua S MartinBiology Department, University of North Carolina, Chapel Hill, North Carolina, USA.
Matthew L KahlscheuerDepartment of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, Michigan, USA.
Ramya KrishnanDepartment of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, Michigan, USA.
John AbelsonDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.
Alain LaederachBiology Department, University of North Carolina, Chapel Hill, North Carolina, USA.
Nils G WalterDepartment of Chemistry, Single Molecule Analysis Group, University of Michigan, Ann Arbor, Michigan, USA.
University of Michigan–Ann Arbor · USUniversity of North Carolina at Chapel Hill · USAnalysis Group (United States) · USUniversity of California, San Francisco · US

Funding

CELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8M
Non-coding RNA structure change in Chronic Obstructive Pulmonary DiseaseR01HL111527 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alain T Laederach, Kevin M Weeks · 2012 to 2026
$6.6M
Structural and functional consequences of disease SNPs on the transcriptomeR01GM101237 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LAEDERACH, ALAIN T · 2012 to 2020
$2.5M
Spliceosome Mechanism Dissected at the Single Molecule LevelR01GM098023 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WALTER, NILS G · 2012 to 2015
$1.3M
BIOSYNTHESIS OF RNASR37GM021119 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI GUTHRIE, CHRISTINE · 1990 to 1999
–
NHLBI NIH HHS R01 HL111527NHLBI NIH HHS R01HL111527-01NIGMS NIH HHS R01 GM098023NIGMS NIH HHS R01GM098023NIGMS NIH HHS R01 GM101237NIGMS NIH HHS R37 GM021119NIGMS NIH HHS T32 GM007315
6 · The paper itself

Abstract

We report Single Molecule Cluster Analysis (SiMCAn), which utilizes hierarchical clustering of hidden Markov modeling-fitted single-molecule fluorescence resonance energy transfer (smFRET) trajectories to dissect the complex conformational dynamics of biomolecular machines. We used this method to study the conformational dynamics of a precursor mRNA during the splicing cycle as carried out by the spliceosome. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify the signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified an open conformation adopted late in splicing by a 3' splice-site mutant, invoking a mechanism for substrate proofreading. SiMCAn enables rapid interpretation of complex single-molecule behaviors and should prove useful for the comprehensive analysis of a plethora of dynamic cellular machines.

Indexed as

Cluster AnalysisRNA SplicingAdenosine TriphosphateCatalytic DomainComputer SimulationFluorescence Resonance Energy TransferFluorescent DyesHumansIntronsMarkov ChainsMutationNucleic Acid ConformationRNA, MessengerRNA PrecursorsRNA Splice SitesSpliceosomesAdenosine TriphosphateFluorescent DyesRNA, MessengerRNA PrecursorsRNA Splice Sites

Identifiers

PMID26414013
PMCPMC4890712
OpenAlexW2222989370

What OpenQuestion holds

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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.