title: Transcriptional pausing controls a rapid antiviral innate immune response in Drosophila.
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.
authors.affiliation: Department of Microbiology, Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, PA 19146, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Gregory
authors.initials: G
authors.lastname: Grant
authors.forename: Leah R
authors.initials: LR
authors.lastname: Sabin
authors.forename: Beth
authors.initials: B
authors.lastname: Gordesky-Gold
authors.forename: Ari
authors.initials: A
authors.lastname: Yasunaga
authors.forename: Mathew
authors.initials: M
authors.lastname: Tudor
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D000818:Animals; D001103:Arboviruses / Q000276:immunology / Q000472:pathogenicity*; D004330:Drosophila / Q000276:immunology / Q000821:virology*; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D012367:RNA, Viral / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D012367:RNA, Viral