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.

人们认为，实际上所有聚腺苷酸化RNA的输出都需要核RNA输出通路的核心成分。在这里，我们耗尽了在人类细胞中核输出中起作用的不同蛋白质，并定量了整个转录组对RNA定位的影响。不同的基因表现出明显不同的敏感性，而NXF1和TREX成分的消耗导致某些转录本牢固保留在细胞核中，而其他转录本则不受影响。具体来说，对于具有长外显子或高A / U含量的单外显子或少量外显子转录本的输出，优先需要NXF1，而TREX复合成分的耗尽会优先影响剪接的和富含G / C的转录本。使用大规模平行报告基因分析 我们鉴定了使转录物依赖于NXF1进行输出的短序列元件，并鉴定了剪接和NXF1的协同作用。这些结果修改了当前的模型，即核输出如何影响人类细胞内RNA的分布。