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Rapid genome-wide recruitment of RNA polymerase II drives transcription, splicing, and translation events during T cell responses.
Cell Rep. 19, 643-654 (2017)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
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
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 19,
Issue: 3,
Pages: 643-654
Publisher
Cell Press
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Peer reviewed