PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Truong, D.J.J. ; Phlairaharn, T. ; Eßwein, B. ; Gruber, C. ; Tümen, D. ; Baligács, E. ; Armbrust, N. ; Vaccaro, F.L. ; Lederer, E.-M. ; Beck, E.M. ; Geilenkeuser, J. ; Göppert, S. ; Krumwiede, L. ; Grätz, C. ; Raffl, G. ; Schwarz, D. ; Zirngibl, M. ; Živanić, M. ; Beyer, M. ; Körner, J.D. ; Santl, T. ; Evsyukov, V.* ; Strauß, T.* ; Schwarz, S.C.* ; Höglinger, G.U.* ; Heutink, P.* ; Doll, S. ; Conrad, M. ; Giesert, F. ; Wurst, W. ; Westmeyer, G.G.

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

Nat. Cell Biol. 23, 652-663 (2021)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
28.824
3.716
1
7
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Messenger-rna; Frontotemporal Dementia; Mapt Expression; Tau Exon-10; Activation; Mutations; Design; Gene; Parkinsonism; Inhibition
Sprache
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Zeitschrift Nature Cell Biology
Quellenangaben Band: 23, Heft: 6, Seiten: 652-663 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Insitute of Synthetic Biomedicine (ISBM)
Institute of Developmental Genetics (IDG)
Institute of Metabolism and Cell Death (MCD)
POF Topic(s) 30205 - Bioengineering and Digital Health
30204 - Cell Programming and Repair
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-509300-001
G-500500-001
G-506900-001
G-500500-009
Förderungen German Federal Ministry of Education and Research (BMBF) through EpiPD
TUM International Graduate School of Science and Engineering (IGSSE, project BIOMAG)
Bavarian Research Network for Molecular Biosystems (BioSysNet)
German Federal Ministry of Education and Research (BMBF) through HIT-Tau
AMPro project 'Aging and Metabolic Programming' of the Helmholtz Association
NOMIS foundation
Deutsche Forschungsgemeinschaft (DFG)
VolkswagenStiftung/Lower Saxony Ministry for Science (Etiology and Therapy of Synucleinopathies and Tauopathies)
Petermax-Muller Foundation
DFG
German Federal Ministry of Education and Research (BMBF) VIP+ program NEUROPROTEKT
Ministry of Science and Higher Education of The Russian Federation
Else Kroner-Fresenius-Stiftung
European Research Council (ERC) under the European Union
European Research Council
DOI 10.1038/s41556-021-00678-x
WOS ID WOS:000657567200001
Scopus ID 85107303441
PubMed ID 34083785
Erfassungsdatum 2021-09-09
[➜Korrektur melden]