The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends

Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal...

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Veröffentlicht in:Genes & development 2015-07, Vol.29 (14), p.1552-1564
Hauptverfasser: Xie, Mingyi, Zhang, Wei, Shu, Mei-Di, Xu, Acer, Lenis, Diana A, DiMaio, Daniel, Steitz, Joan A
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container_end_page 1564
container_issue 14
container_start_page 1552
container_title Genes & development
container_volume 29
creator Xie, Mingyi
Zhang, Wei
Shu, Mei-Di
Xu, Acer
Lenis, Diana A
DiMaio, Daniel
Steitz, Joan A
description Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3' end processing signal (3' box), generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box-like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3' end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing, HVS pre-miRNA 3' end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.
doi_str_mv 10.1101/gad.266973.115
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subjects Gene Knockdown Techniques
HEK293 Cells
HeLa Cells
Herpesvirus 2, Saimiriine - genetics
Herpesvirus 2, Saimiriine - metabolism
Herpesvirus saimiri
Host-Pathogen Interactions - genetics
Humans
Immunoprecipitation
MicroRNAs - chemistry
MicroRNAs - genetics
MicroRNAs - metabolism
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Research Paper
RNA 3' End Processing - genetics
RNA 3' End Processing - physiology
RNA Precursors - genetics
RNA Precursors - metabolism
RNA, Small Nuclear - metabolism
Transcription, Genetic
title The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3' ends
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