Tau-induced nuclear envelope invagination causes a toxic accumulation of mRNA in Drosophila

Garrett L. Cornelison, Simon A. Levy, Tyler Jenson, Bess Frost

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The nucleus is a spherical dual-membrane bound organelle that encapsulates genomic DNA. In eukaryotes, messenger RNAs (mRNA) are transcribed in the nucleus and transported through nuclear pores into the cytoplasm for translation into protein. In certain cell types and pathological conditions, nuclei harbor tubular invaginations of the nuclear envelope known as the “nucleoplasmic reticulum.” Nucleoplasmic reticulum expansion has recently been established as a mediator of neurodegeneration in tauopathies, including Alzheimer's disease. While the presence of pore-lined, cytoplasm-filled, nuclear envelope invaginations has been proposed to facilitate the rapid export of RNAs from the nucleus to the cytoplasm, the functional significance of nuclear envelope invaginations in regard to RNA export in any disorder is currently unknown. Here, we report that polyadenylated RNAs accumulate within and adjacent to tau-induced nuclear envelope invaginations in a Drosophila model of tauopathy. Genetic or pharmacologic inhibition of RNA export machinery reduces accumulation of polyadenylated RNA within and adjacent to nuclear envelope invaginations and reduces tau-induced neuronal death. These data are the first to point toward a possible role for RNA export through nuclear envelope invaginations in the pathogenesis of a neurodegenerative disorder and suggest that nucleocytoplasmic transport machinery may serve as a possible novel class of therapeutic targets for the treatment of tauopathies.

Original languageEnglish (US)
Article numbere12847
JournalAging cell
Volume18
Issue number1
DOIs
StatePublished - Feb 2019

Keywords

  • RNA
  • nuclear export
  • nucleocytoplasmic transport
  • nucleus
  • tau
  • tauopathy

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint

Dive into the research topics of 'Tau-induced nuclear envelope invagination causes a toxic accumulation of mRNA in Drosophila'. Together they form a unique fingerprint.

Cite this