Trypanosomes can initiate nuclear export co-transcriptionally
Trypanosomes can initiate nuclear export co-transcriptionally
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DOI：
10.1093/nar/gky1136
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发表时间：
2019-01-10
影响因子：
14.9
通讯作者：
Kramer, Susanne
中科院分区：
文献类型：
--
作者：
Goos, Carina;Dejung, Mario;Kramer, Susanne
核膜是重要的信使RNA（mRNA）监视系统。在酵母和人类中，几个控制系统平行地起作用以防止未加工的mRNA的核输出。锥虫缺乏与大多数相关蛋白质的同源物，并且它们的核mRNA代谢是非常规的，例如多顺反子转录和通过反式剪接的mRNA加工。我们在这里可视化核出口锥虫内和分子间多色单分子荧光原位杂交。我们发现，与其他真核生物形成鲜明对比的是，核输出的启动既不需要完成转录也不需要剪接。然而，我们发现，大多数未剪接的mRNA被阻止到达细胞核远端的细胞质，而是积累在细胞质核周边颗粒（NPG）的核周边。通过电子显微镜和蛋白质组学对NPG的进一步表征显示，颗粒位于核孔的细胞质位点，并且含有大多数细胞质RNA结合蛋白，但没有主要的翻译起始因子，这与防止错误mRNA到达翻译的功能一致。我们的数据表明，锥虫调节核输出的完成，而不是启动。对任何生物体的核出口管制仍然知之甚少，所述管制方式可能不仅限于锥虫。
The nuclear envelope serves as important messenger RNA (mRNA) surveillance system. In yeast and human, several control systems act in parallel to prevent nuclear export of unprocessed mRNAs. Trypanosomes lack homologues to most of the involved proteins and their nuclear mRNA metabolism is non-conventional exemplified by polycistronic transcription and mRNA processing by trans-splicing. We here visualized nuclear export in trypanosomes by intra- and intermolecular multi-colour single molecule FISH. We found that, in striking contrast to other eukaryotes, the initiation of nuclear export requires neither the completion of transcription nor splicing. Nevertheless, we show that unspliced mRNAs are mostly prevented from reaching the nucleus-distant cytoplasm and instead accumulate at the nuclear periphery in cytoplasmic nuclear periphery granules (NPGs). Further characterization of NPGs by electron microscopy and proteomics revealed that the granules are located at the cytoplasmic site of the nuclear pores and contain most cytoplasmic RNA-binding proteins but none of the major translation initiation factors, consistent with a function in preventing faulty mRNAs from reaching translation. Our data indicate that trypanosomes regulate the completion of nuclear export, rather than the initiation. Nuclear export control remains poorly understood, in any organism, and the described way of control may not be restricted to trypanosomes.