Evidence map›Paper›PMID 37178687›Full record

ArticleCell2023

Sites of transcription initiation drive mRNA isoform selection.

Carlos Alfonso-Gonzalez, Ivano Legnini, Sarah Holec, Laura Arrigoni, Hasan Can Ozbulut, Fernando Mateos, David Koppstein, Agnieszka Rybak-Wolf, Ulrike Bönisch, Nikolaus Rajewsky and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Carlos Alfonso-GonzalezMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, Albert Ludwig University, 79104 Freiburg, Germany; International Max Planck Research School for Molecular and Cellular Biology (IMPRS-MCB), 79108 Freiburg, Germany.
Ivano LegniniLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Sarah HolecMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Laura ArrigoniMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Hasan Can OzbulutMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Faculty of Biology, Albert Ludwig University, 79104 Freiburg, Germany.
Fernando MateosMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
David KoppsteinMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Agnieszka Rybak-WolfOrganoid Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany.
Ulrike BönischMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Nikolaus RajewskyLaboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 10115 Berlin, Germany; Charité - Universitätsmedizin, Charitépl. 1, 10117 Berlin, Germany; German Center for Cardiovascular Research (DZHK), Site Berlin, Berlin, Germany; NeuroCure Cluster of Excellence, Berlin, Germany; German Cancer Consortium (DKTK); National Center for Tumor Diseases (NCT), Site Berlin, Berlin, Germany.
Valérie HilgersMax-Planck-Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany; Signalling Research Centre CIBSS, University of Freiburg, Schänzlestraße 18, 79104 Freiburg, Germany. Electronic address: hilgers@ie-freiburg.mpg.de.
Max Planck Institute of Immunobiology and Epigenetics · DEMax Delbrück Center · DENational Center for Tumor Diseases · DEUniversity of Freiburg · DE

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Annette L. Parks · 2014 to 2026
$13.5M
Drosophila Transgenic RNAi Resource ProjectR01GM084947 · NIGMS · HARVARD MEDICAL SCHOOL · PI PERRIMON, NORBERT · 2008 to 2019
$9.8M
NIGMS NIH HHS R01 GM084947NIH HHS P40 OD018537
6 · The paper itself

Abstract

The generation of distinct messenger RNA isoforms through alternative RNA processing modulates the expression and function of genes, often in a cell-type-specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing, and 3' end site selection. Applying long-read sequencing to accurately represent even the longest transcripts from end to end, we quantify mRNA isoforms in Drosophila tissues, including the transcriptionally complex nervous system. We find that in Drosophila heads, as well as in human cerebral organoids, 3' end site choice is globally influenced by the site of transcription initiation (TSS). "Dominant promoters," characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as p300/CBP loss disrupted the 3' end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity.

Indexed as

Alternative SplicingRNA IsoformsTranscription Initiation SiteHumansPolyadenylationPromoter Regions, GeneticRNA, MessengerRNA IsoformsRNA, Messenger5ʹ-3ʹ couplingalternative polyadenylationDrosophilahuman brain organoidslong-read sequencingmRNA isoformnervous systemp300/CBPtranscriptiontranscription start site

Identifiers

PMID37178687
PMCPMC10228280
OpenAlexW4376275151

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.