Evidence map›Paper›PMID 25541195›Full record

ArticleNucleic acids research2015

Considering the kinetics of mRNA synthesis in the analysis of the genome and epigenome reveals determinants of co-transcriptional splicing.

Jeremy C Davis-Turak, Karmel Allison, Maxim N Shokhirev, Petr Ponomarenko, Lev S Tsimring, Christopher K Glass, Tracy L Johnson, Alexander Hoffmann

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Nascent RNA and the Coordination of Splicing with Transcription.Cold Spring Harbor perspectives in biology · 2019
    Review
  5. Article
  6. Article
  7. The determinants of alternative RNA splicing in human cells.Molecular genetics and genomics : MGG · 2017
    Review
  8. Perfect timing: splicing and transcription rates in living cells.Wiley interdisciplinary reviews. RNA · 2017
    Review
  9. Signaling via the NFκB system.Wiley interdisciplinary reviews. Systems biology and medicine · 2016
    Review
  10. Article
  11. Review
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

8 authors.

Jeremy C Davis-TurakSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Karmel AllisonSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Maxim N ShokhirevSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Petr PonomarenkoSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Lev S TsimringSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA BioCircuits Institute, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Christopher K GlassSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Tracy L JohnsonSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, CA 90095, USA ahoffmann@ucla.edu.
Alexander HoffmannSan Diego Center for Systems Biology (SDCSB), University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA BioCircuits Institute, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California at Los Angeles, Los Angeles, CA 90095, USA Institute for Quantitative and Computational Biosciences (QCB), University of California at Los Angeles, Los Angeles, CA 90095, USA ahoffmann@ucla.edu.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
"Ribonomics" of Gene Regulation to predict Innate Immune ResponsesU01HG007912 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L, HOFFMANN, ALEXANDER · 2015 to 2017
$5.8M
Eukaryotic RNA Processing and Chromatin ModificationR01GM085474 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOHNSON, TRACY L · 2010 to 2021
$2.6M
Epigenomic control of RNA splicingR01ES024995 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER, XING, YI · 2014 to 2015
$616k
NCI NIH HHS P30 CA023100NHGRI NIH HHS U01 HG007912NIEHS NIH HHS R01 ES024995NIEHS NIH HHS R01ES024995NIGMS NIH HHS P50 GM085764NIGMS NIH HHS R01 GM085474
6 · The paper itself

Abstract

When messenger RNA splicing occurs co-transcriptionally, the potential for kinetic control based on transcription dynamics is widely recognized. Indeed, perturbation studies have reported that when transcription kinetics are perturbed genetically or pharmacologically splice patterns may change. However, whether kinetic control is contributing to the control of splicing within the normal range of physiological conditions remains unknown. We examined if the kinetic determinants for co-transcriptional splicing (CTS) might be reflected in the structure and expression patterns of the genome and epigenome. To identify and then quantitatively relate multiple, simultaneous CTS determinants, we constructed a scalable mathematical model of the kinetic interplay of RNA synthesis and CTS and parameterized it with diverse next generation sequencing (NGS) data. We thus found a variety of CTS determinants encoded in vertebrate genomes and epigenomes, and that these combine variously for different groups of genes such as housekeeping versus regulated genes. Together, our findings indicate that the kinetic basis of splicing is functionally and physiologically relevant, and may meaningfully inform the analysis of genomic and epigenomic data to provide insights that are missed when relying on statistical approaches alone.

Indexed as

Models, GeneticRNA SplicingTranscription, GeneticAnimalsComputer SimulationEpigenesis, GeneticGenes, EssentialGenomicsHumansKineticsMiceRNA, MessengerRNA Polymerase IISequence Analysis, RNARNA, MessengerRNA Polymerase II

Identifiers

PMID25541195
PMCPMC4333389

What OpenQuestion holds

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LicenceCC BY-NC
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.