Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

 
 
DownloadE-Mail
  Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation

Bose, D., Neumann, A., Timmermann, B., Meinke, S., & Heyd, F. (2019). Differential Interleukin-2 Transcription Kinetics Render Mouse but Not Human T Cells Vulnerable to Splicing Inhibition Early after Activation. Molecular and Cellular Biology (Washington, DC), 39(16): e00035-19. doi:10.1128/MCB.00035-19.

Item is

Basisdaten

einblenden: ausblenden:
Genre: Zeitschriftenartikel

Dateien

einblenden: Dateien
ausblenden: Dateien
:
Bose_2019.pdf (Verlagsversion), 4MB
Name:
Bose_2019.pdf
Beschreibung:
-
OA-Status:
Sichtbarkeit:
Öffentlich
MIME-Typ / Prüfsumme:
application/pdf / [MD5]
Technische Metadaten:
Copyright Datum:
-
Copyright Info:
© 2019 American Society for Microbiology
Lizenz:
-

Externe Referenzen

einblenden:

Urheber

einblenden:
ausblenden:
 Urheber:
Bose, Debojit , Autor
Neumann, Alexander , Autor
Timmermann, Bernd1, Autor           
Meinke, Stefan , Autor
Heyd, Florian , Autor
Affiliations:
1Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

Inhalt

einblenden:
ausblenden:
Schlagwörter: RNA splicing; T cell activation; gene expression; interleukin-2
 Zusammenfassung: T cells are nodal players in the adaptive immune response against pathogens and malignant cells. Alternative splicing plays a crucial role in T cell activation, which is analyzed mainly at later time points upon stimulation. Here we have discovered a 2-h time window early after stimulation where optimal splicing efficiency or, more generally, gene expression efficiency is crucial for successful T cell activation. Reducing the splicing efficiency at 4 to 6 h poststimulation significantly impaired murine T cell activation, which was dependent on the expression dynamics of the Egr1-Nab2-interleukin-2 (IL-2) pathway. This time window overlaps the time of peak IL-2 de novo transcription, which, we suggest, represents a permissive time window in which decreased splicing (or transcription) efficiency reduces mature IL-2 production, thereby hampering murine T cell activation. Notably, the distinct expression kinetics of the Egr1-Nab2-IL-2 pathway between mouse and human render human T cells refractory to this vulnerability. We propose that the rational temporal modulation of splicing or transcription during peak de novo expression of key effectors can be used to fine-tune stimulation-dependent biological outcomes. Our data also show that critical consideration is required when extrapolating mouse data to the human system in basic and translational research.

Details

einblenden:
ausblenden:
Sprache(n): eng - English
 Datum: 2019-05-282019-07-292019-08-15
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1128/MCB.00035-19
PMID: 31160491
 Art des Abschluß: -

Veranstaltung

einblenden:

Entscheidung

einblenden:

Projektinformation

einblenden:

Quelle 1

einblenden:
ausblenden:
Titel: Molecular and Cellular Biology (Washington, DC)
  Andere : Mol Cell Biol
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: American Society for Microbiology (ASM)
Seiten: - Band / Heft: 39 (16) Artikelnummer: e00035-19 Start- / Endseite: - Identifikator: ISSN: 0270-7306
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188