English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  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

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0004-DC2C-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-DC2D-3
Genre: Journal Article

Files

show Files
hide Files
:
Bose_2019.pdf (Publisher version), 4MB
Name:
Bose_2019.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019 American Society for Microbiology
License:
-

Locators

show

Creators

show
hide
 Creators:
Bose, Debojit , Author
Neumann, Alexander , Author
Timmermann, Bernd1, Author              
Meinke, Stefan , Author
Heyd, Florian , Author
Affiliations:
1Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

Content

show
hide
Free keywords: RNA splicing; T cell activation; gene expression; interleukin-2
 Abstract: 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

show
hide
Language(s): eng - English
 Dates: 2019-05-282019-07-292019-08-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1128/MCB.00035-19
PMID: 31160491
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Molecular and Cellular Biology (Washington, DC)
  Other : Mol Cell Biol
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: American Society for Microbiology (ASM)
Pages: - Volume / Issue: 39 (16) Sequence Number: e00035-19 Start / End Page: - Identifier: ISSN: 0270-7306
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188