期刊
CELL REPORTS
卷 19, 期 3, 页码 643-654出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.069
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- Deutsche Forschungs gemeinschaft (DFG) [FR2938/7-1, CRC 1123 (Z2), GL 870/1-1]
- German Center for Diabetes Research (DZD), Helmholtz Zentrum Munchen
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 genomewide temporal dynamics for similar to 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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