Although splicing is a major driver of RNA nuclear export, many intronless RNAs are efficiently exported to the cytoplasm through poorly characterized mechanisms. For example, GC-rich sequences promote nuclear export in a splicing-independent manner, but how GC content is recognized and coupled to nuclear export is unknown. Here, we developed a genome-wide screening strategy to investigate the mechanism of export of NORAD, an intronless cytoplasmic long noncoding RNA (lncRNA). This screen revealed an RNA binding protein, RBM33, that directs the nuclear export of NORAD and numerous other transcripts. RBM33 directly binds substrate transcripts and recruits components of the TREX–NXF1/NXT1 RNA export pathway. Interestingly, high GC content emerged as the feature that specifies RBM33-dependent nuclear export. Accordingly, RBM33 directly binds GC-rich elements in target transcripts. These results provide a broadly applicable strategy for the genetic dissection of nuclear export mechanisms and reveal a long-sought nuclear export pathway for transcripts with GC-rich sequences.

中文翻译：

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RBM33 指导含有富含 GC 元素的转录本的核输出

尽管剪接是 RNA 核输出的主要驱动力，但许多无内含子 RNA 通过特征不明确的机制有效地输出到细胞质。例如，富含 GC 的序列以独立于剪接的方式促进核输出，但如何识别 GC 内容并将其与核输出耦合尚不清楚。在这里，我们开发了一种全基因组筛选策略来研究 NORAD 的输出机制，NORAD是一种无内含子的细胞质长非编码 RNA (lncRNA)。该筛选揭示了一种 RNA 结合蛋白 RBM33，它指导NORAD的核输出和许多其他成绩单。RBM33 直接结合底物转录物并募集 TREX-NXF1/NXT1 RNA 输出途径的组分。有趣的是，高 GC 含量成为指定依赖 RBM33 的核输出的特征。因此，RBM33 直接结合目标转录本中富含 GC 的元素。这些结果为核输出机制的遗传剖析提供了广泛适用的策略，并揭示了具有 GC 丰富序列的转录本长期寻求的核输出途径。