Evidence map›Paper›PMID 34083785›Full record

ArticleNature cell biology2021

Non-invasive and high-throughput interrogation of exon-specific isoform expression.

Dong-Jiunn Jeffery Truong, Teeradon Phlairaharn, Bianca Eßwein, Christoph Gruber, Deniz Tümen, Enikő Baligács, Niklas Armbrust, Francesco Leandro Vaccaro, Eva-Maria Lederer, Eva Magdalena Beck and 21 more

Open access · hybridAbstract read
In one paragraph

Article in Nature cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Cross-tissue immune profiling of APOE ε4 reveals early dysregulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  11. Disease modification in Parkinsonism: obstacles and ways forward.Journal of neural transmission (Vienna, Austria : 1996) · 2022
    Review
  12. Tissue-specific expression of myosin phosphatase subunits and isoforms in smooth muscle of mice and humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2022
    Article
  13. 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

31 authors at 2 institutions in 2 countries.

Dong-Jiunn Jeffery TruongInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0003-1722-8573
Teeradon PhlairaharnInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0001-6031-0578
Bianca EßweinInstitute of Developmental Genetics, Helmholtz Zentrum München, Oberschleißheim, Germany.
Christoph GruberInstitute of Developmental Genetics, Helmholtz Zentrum München, Oberschleißheim, Germany.
Deniz TümenInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Enikő BaligácsInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Niklas ArmbrustInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Francesco Leandro VaccaroInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Eva-Maria LedererInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0002-1220-1040
Eva Magdalena BeckInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Julian GeilenkeuserInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Simone GöppertInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Luisa KrumwiedeInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Christian GrätzInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Gerald RafflInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0003-0210-0286
Dominic SchwarzInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Martin ZirngiblInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0003-4485-8423
Milica ŽivanićInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Maren BeyerInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Johann Dietmar KörnerInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Tobias SantlInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany.
Valentin EvsyukovGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Tabea StraußGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Sigrid C SchwarzGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Günter U HöglingerGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.ORCID http://orcid.org/0000-0001-7587-6187
Peter HeutinkDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Sebastian DollInstitute of Metabolism and Cell Death, Helmholtz Zentrum München, Oberschleißheim, Germany.
Marcus ConradInstitute of Metabolism and Cell Death, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0003-1140-5612
Florian GiesertInstitute of Developmental Genetics, Helmholtz Zentrum München, Oberschleißheim, Germany.ORCID http://orcid.org/0000-0001-6825-8858
Wolfgang WurstInstitute of Developmental Genetics, Helmholtz Zentrum München, Oberschleißheim, Germany.
Gil Gregor WestmeyerInstitute for Synthetic Biomedicine, Helmholtz Zentrum München, Oberschleißheim, Germany. gil.westmeyer@tum.de.ORCID http://orcid.org/0000-0001-7224-8919
Helmholtz Zentrum München · DEGerman Center for Neurodegenerative Diseases · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Expression of exon-specific isoforms from alternatively spliced mRNA is a fundamental mechanism that substantially expands the proteome of a cell. However, conventional methods to assess alternative splicing are either consumptive and work-intensive or do not quantify isoform expression longitudinally at the protein level. Here, we therefore developed an exon-specific isoform expression reporter system (EXSISERS), which non-invasively reports the translation of exon-containing isoforms of endogenous genes by scarlessly excising reporter proteins from the nascent polypeptide chain through highly efficient, intein-mediated protein splicing. We applied EXSISERS to quantify the inclusion of the disease-associated exon 10 in microtubule-associated protein tau (MAPT) in patient-derived induced pluripotent stem cells and screened Cas13-based RNA-targeting effectors for isoform specificity. We also coupled cell survival to the inclusion of exon 18b of FOXP1, which is involved in maintaining pluripotency of embryonic stem cells, and confirmed that MBNL1 is a dominant factor for exon 18b exclusion. EXSISERS enables non-disruptive and multimodal monitoring of exon-specific isoform expression with high sensitivity and cellular resolution, and empowers high-throughput screening of exon-specific therapeutic interventions.

Indexed as

Alternative SplicingHigh-Throughput Screening AssaysProteomicsRNA StabilityCRISPR-Cas SystemsExonsForkhead Transcription FactorsHEK293 CellsHumansInduced Pluripotent Stem CellsProtein IsoformsProteomeRepressor ProteinsRNA-Binding ProteinsRNA, MessengerSingle-Cell AnalysisForkhead Transcription FactorsFOXP1 protein, humanMAPT protein, humanMBNL1 protein, humanProtein IsoformsProteomeRepressor ProteinsRNA-Binding ProteinsRNA, Messengertau Proteins

Identifiers

PMID34083785
PMCPMC8189919
OpenAlexW3165600341

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.