Rapid Genome-wide Recruitment of RNA Polymerase II Drives Transcription, Splicing, and Translation Events during T Cell Responses

Kathrin Davari, Johannes Lichti, Christian Gallus, Franziska Greulich, N. Henriette Uhlenhaut, Matthias Heinig, Caroline C. Friedel, Elke Glasmacher

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Activation of immune cells results in rapid functional changes, but how such fast changes are accomplished remains enigmatic. By combining time courses of 4sU-seq, RNA-seq, ribosome profiling (RP), and RNA polymerase II (RNA Pol II) ChIP-seq during T cell activation, we illustrate genome-wide temporal dynamics for ∼10,000 genes. This approach reveals not only immediate-early and posttranscriptionally regulated genes but also coupled changes in transcription and translation for >90% of genes. Recruitment, rather than release of paused RNA Pol II, primarily mediates transcriptional changes. This coincides with a genome-wide temporary slowdown in cotranscriptional splicing, even for polyadenylated mRNAs that are localized at the chromatin. Subsequent splicing optimization correlates with increasing Ser-2 phosphorylation of the RNA Pol II carboxy-terminal domain (CTD) and activation of the positive transcription elongation factor (pTEFb). Thus, rapid de novo recruitment of RNA Pol II dictates the course of events during T cell activation, particularly transcription, splicing, and consequently translation.

Original languageEnglish
Pages (from-to)643-654
Number of pages12
JournalCell Reports
Volume19
Issue number3
DOIs
StatePublished - 18 Apr 2017
Externally publishedYes

Keywords

  • 4sU
  • H3K36
  • RNA Pol II
  • Ser-2 RNA Pol II
  • Ser-5 RNA Pol II
  • T cell activation
  • cotranscriptional splicing
  • immediate-early genes
  • immune response
  • ribosome profiling

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