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


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 languageEnglish
Pages (from-to)251-267.e6
JournalMolecular Cell
Issue number2
StatePublished - 16 Jul 2020
Externally publishedYes

Bibliographical note

Funding Information:
We thank Schragi Schwartz, Shalev Itzkovitz, Yaron Shav-Tal, and members of the Ulitsky lab for comments on the manuscript and helpful discussions. We thank Shalev Itzkovitz for the kind gift of smFISH probes and help with the smFISH protocol. We thank Joan Steitz for the kind gift of the beta-globin Δintrons plasmid. We also thank Raya Eilam for the help with the smFISH protocol and imaging and Ofra Golani for help with image analysis. We thank Florian Edhard for the support in performing GRAND-SLAM analysis and Florian Mueller for the support in using FishQuant. This research was supported by grants to I.U. from the Israeli Science Foundation (ISF) (grant 852/19 ), the ISF -Natural Science Foundation of China (NSFC) joint research program (grant 2406/18), the Germany-Israeli Foundation for Scientific Research and Development (grant I-144-417.5-2017 ), the Israeli Ministry of Health as part of the ERA-NET localMND, and the Azrieli Institute for Systems Biology. I.U. is incumbent of the Sygnet Career Development Chair for Bioinformatics.

Publisher Copyright:
© 2020 Elsevier Inc.


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

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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