Transcriptional pausing controls a rapid antiviral innate immune response in Drosophila

Jie Xu, Gregory Grant, Leah R. Sabin, Beth Gordesky-Gold, Ari Yasunaga, Mathew Tudor, Sara Cherry

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Abstract

Innate immune responses are characterized by precise gene expression whereby gene subsets are temporally induced to limit infection, although the mechanisms involved are incompletely understood. We show that antiviral immunity in Drosophila requires the transcriptional pausing pathway, including negative elongation factor (NELF) that pauses RNA polymerase II (Pol II) and positive elongation factor b (P-TEFb), which releases paused Pol II to produce full-length transcripts. We identify a set of genes that is rapidly transcribed upon arbovirus infection, including components of antiviral pathways (RNA silencing, autophagy, JAK/STAT, Toll, and Imd) and various Toll receptors. Many of these genes require P-TEFb for expression and exhibit pausing-associated chromatin features. Furthermore, transcriptional pausing is critical for antiviral immunity in insects because NELF and P-TEFb are required to restrict viral replication in adult flies and vector mosquito cells. Thus, transcriptional pausing primes virally induced genes to facilitate rapid gene induction and robust antiviral responses.

Original languageEnglish (US)
Pages (from-to)531-543
Number of pages13
JournalCell Host and Microbe
Volume12
Issue number4
DOIs
Publication statusPublished - Oct 18 2012

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Xu, J., Grant, G., Sabin, L. R., Gordesky-Gold, B., Yasunaga, A., Tudor, M., & Cherry, S. (2012). Transcriptional pausing controls a rapid antiviral innate immune response in Drosophila. Cell Host and Microbe, 12(4), 531-543. https://doi.org/10.1016/j.chom.2012.08.011