Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
Mol Cell. 2020 Jul 16;79(2):251-267.e6. doi: 10.1016/j.molcel.2020.05.013. Epub 2020 Jun 5.
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.
核 RNA 输出途径的核心成分被认为几乎是所有多聚腺苷酸化 RNA 输出所必需的。在这里，我们耗尽了在人类细胞中发挥核输出作用的不同蛋白质，并定量分析了 RNA 定位的转录组范围的后果。不同的基因表现出明显的可变敏感性，NXF1 和 TREX 成分的耗竭导致一些转录物强烈保留在核内，而其他转录物不受影响。具体来说，NXF1 优先用于长外显子或高 A/U 含量的单外显子或少数外显子转录物的输出，而 TREX 复合物成分的耗竭则优先影响剪接和富含 G/C 的转录物。使用大规模平行报告基因检测，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。这些结果修正了核输出如何塑造人类细胞内 RNA 分布的现有模型。
