Coordination of tRNA nuclear export with processing of tRNA
Coordination of tRNA nuclear export with processing of tRNA
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DOI：
10.1017/s1355838299982134
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发表时间：
1999-04-01
期刊：
影响因子：
4.5
通讯作者：
Görlich, D
中科院分区：
文献类型：
--
作者：
Lipowsky, G;Bischoff, FR;Görlich, D
真核生物的tRNA在细胞核内合成，需要输出到细胞质中，在细胞质中发挥翻译作用，tRNA输出由export -t介导，export -t直接高亲和力结合tRNA。trna最初作为前体分子合成。功能性tRNA的成熟发生在细胞核中，在输出之前，包括5‘和3’末端的修剪，3' CCA末端的转录后添加，核苷修饰，在某些情况下剪接。在这里，我们解决tRNA成熟如何与出口协调的问题，从而如何避免无活性成熟中间体的细胞质积累。原则上，这可以通过未成熟tRNA的核保留或完全成熟形式的选择性输出来实现。我们发现export -t对正确处理的5‘和3’端和核苷修饰的tRNA有强烈的偏好。因此，通过export -t识别tRNA可以被认为是tRNA出口之前这些成熟步骤的质量控制机制。然而，令人惊讶的是，export -t可以有效地结合未剪接的tRNA，当剪接速率较慢时，含有内含子的tRNA被输出。在表征输出-t/tRNA相互作用的过程中，我们发现输出-t识别tRNA中在原核和真核tRNA之间保守的特征。我们的数据表明，正确的tRNA形状、5‘和3’末端以及tpsi C环对于输出- T结合至关重要。
Eukaryotic tRNAs are synthesized in the nucleus and need to be exported to the cytoplasm where they function in translation, tRNA export is mediated by exportin-t, which binds tRNA directly and with high affinity. tRNAs are initially synthesized as precursor molecules. Maturation to functional tRNA takes place in the nucleus, precedes export, and includes trimming of the 5' and 3' ends, posttranscriptional addition of the 3' CCA end, nucleoside modifications, and in some cases splicing. Here we address the question of how tRNA maturation is coordinated with export and thus how cytoplasmic accumulation of inactive maturation intermediates is avoided. This could, in principle, be achieved by nuclear retention of immature tRNA or by selective export of the fully mature form. We show that exportin-t has a strong preference for tRNA with correctly processed 5' and 3' ends and nucleoside modification. tRNA recognition by exportin-t can thus be considered as a quality control mechanism for these maturation steps prior to tRNA export. Surprisingly however, exportin-t can efficiently bind unspliced tRNA and intron-containing tRNA is exported when the rate of splicing is slow. During characterization of the exportin-t/tRNA interaction we found that exportin-t recognizes features in the tRNA that ave conserved between prokaryotic and eukaryotic tRNAs. Our data suggest that correct tRNA shape, the 5' and 3' terminal ends, and the T Psi C loop are critical for exportin-t binding.