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

• Published in: Molecular cell Vol. 79; no. 2; pp. 251 - 267.e6
• Main Authors: Zuckerman, Binyamin, Ron, Maya, Mikl, Martin, Segal, Eran, Ulitsky, Igor
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 16.07.2020
• Subjects: long noncoding RNAs; nuclear export; NXF1; post-transcriptional regulation; RNA localization; splicing; TREX; NXF1; long noncoding RNAs; nuclear export; TREX; post-transcriptional regulation; RNA localization; splicing
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2020.05.013

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. [Display omitted] •Depletion of NXF1 and TREX retains in the nucleus different transcript groups•Transcripts with few or long exons are preferentially dependent on NXF1•G/C-rich, 5′-biased, and m6A-modified regions drive single-exon transcript export•Splicing efficiency affects export in a largely NXF1-independent manner Zuckerman et al. study the consequences of depletion of core components of the nuclear RNA export pathway in human cells. Different components are required for nuclear export of distinct transcript sets. Gene architecture, sequence composition, RNA secondary structure, RNA modifications, and certain sequence motifs are associated with this selective dependency.