Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex

Binyamin Zuckerman, Maya Ron, Martin Mikl, Eran Segal, Igor Ulitsky

Research output: Contribution to journalArticlepeer-review

Abstract

The core components of the nuclear RNA export pathway are thought to be required for export of virtually all polyadenylated RNAs. Here, we depleted different proteins that act in nuclear export in human cells and quantified the transcriptome-wide consequences on RNA localization. Different genes exhibited substantially variable sensitivities, with depletion of NXF1 and TREX components causing some transcripts to become strongly retained in the nucleus while others were not affected. Specifically, NXF1 is preferentially required for export of single- or few-exon transcripts with long exons or high A/U content, whereas depletion of TREX complex components preferentially affects spliced and G/C-rich transcripts. Using massively parallel reporter assays, we identified short sequence elements that render transcripts dependent on NXF1 for their export and identified synergistic effects of splicing and NXF1. These results revise the current model of how nuclear export shapes the distribution of RNA within human cells.

Original languageAmerican English
Pages (from-to)251-267.e6
JournalMolecular Cell
Volume79
Issue number2
DOIs
StatePublished - 16 Jul 2020
Externally publishedYes

Keywords

  • NXF1
  • RNA localization
  • TREX
  • long noncoding RNAs
  • nuclear export
  • post-transcriptional regulation
  • splicing

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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