RBM33 directs the nuclear export of transcripts containing GC-rich elements.
RBM33 directs the nuclear export of transcripts containing GC-rich elements.
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DOI：
10.1101/gad.349456.122
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发表时间：
2022-05-01
影响因子：
10.5
通讯作者：
Mendell, Joshua T.
中科院分区：
文献类型：
--
作者：
Thomas, Anu;Rehfeld, Frederick;Zhang, He;Chang, Tsung-Cheng;Goodarzi, Mohammad;Gillet, Frank;Mendell, Joshua T.
在这项研究中，托马斯等人开发了一种全基因组筛选策略来研究NORAD（一种无内含子的细胞质长非编码RNA（lncRNA））的输出机制，并发现了一种RNA结合蛋白RBM 33，它指导NORAD和许多其他转录物的核输出。这些结果提供了一个广泛适用的战略，为核出口机制的遗传解剖，并揭示了一个长期寻求的核出口途径与GC丰富的序列的成绩单。尽管剪接是RNA核输出的主要驱动因素，但许多无内含子RNA通过特征不清的机制有效地输出到细胞质。例如，富含GC的序列以不依赖于剪接的方式促进核输出，但GC含量如何被识别并与核输出偶联尚不清楚。在这里，我们开发了一个全基因组筛选策略，调查出口的NORAD，一个无内含子的细胞质长非编码RNA（lncRNA）的机制。该筛选揭示了RNA结合蛋白RBM 33，其指导NORAD和许多其他转录物的核输出。RBM 33直接结合底物转录物并募集TREX-NXF 1/NXT 1 RNA输出途径的组分。有趣的是，高GC含量作为指定RBM 33依赖性核输出的特征出现。因此，RBM 33直接结合靶转录物中富含GC的元件。这些结果提供了一个广泛适用的战略，为核出口机制的遗传解剖，并揭示了一个长期寻求的核出口途径与GC丰富的序列的成绩单。
In this study, Thomas et al. developed a genome-wide screening strategy to investigate the mechanism of export of NORAD, an intronless cytoplasmic long noncoding RNA (lncRNA), and found an RNA binding protein, RBM33, that directs the nuclear export of NORAD and numerous other 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. 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.
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