The RNA helicase UPF1 associates with mRNAs co-transcriptionally and is required for the release of mRNAs from gene loci

Elife. 2019 Mar 25:8:e41444. doi: 10.7554/eLife.41444.

Abstract

UPF1 is an RNA helicase that is required for nonsense-mediated mRNA decay (NMD) in eukaryotes, and the predominant view is that UPF1 mainly operates on the 3'UTRs of mRNAs that are directed for NMD in the cytoplasm. Here we offer evidence, obtained from Drosophila, that UPF1 constantly moves between the nucleus and cytoplasm by a mechanism that requires its RNA helicase activity. UPF1 is associated, genome-wide, with nascent RNAs at most of the active Pol II transcription sites and at some Pol III-transcribed genes, as demonstrated microscopically on the polytene chromosomes of salivary glands and by ChIP-seq analysis in S2 cells. Intron recognition seems to interfere with association and translocation of UPF1 on nascent pre-mRNAs, and cells depleted of UPF1 show defects in the release of mRNAs from transcription sites and their export from the nucleus.

Keywords: D. melanogaster; NMD; RNA helicases; Transcription; chromosomes; gene expression; mRNA export; polytene chromosomes; splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / metabolism*
  • RNA Helicases / metabolism*
  • RNA, Messenger / metabolism*
  • Transcription, Genetic*

Substances

  • Drosophila Proteins
  • RNA, Messenger
  • Upf1 protein, Drosophila
  • RNA Helicases

Associated data

  • GEO/GSE116808
  • GEO/GSE116806
  • GEO/GSE116807