RNA splicing promotes translation and RNA surveillance
RNA splicing promotes translation and RNA surveillance
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DOI：
10.1038/nsmb980
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发表时间：
2005-09-01
影响因子：
16.8
通讯作者：
Wilkinson, MF
中科院分区：
文献类型：
--
作者：
Gudikote, JP;Imam, JS;Wilkinson, MF
含有提前终止密码子(PTC或无意义密码子)的异常mRNAs通过无意义介导的mRNA衰变(NMD)途径降解。转录自在淋巴细胞发育过程中自然获得PTCs的基因的mRNAs被PTCs强烈下调。在这里，我们表明，对于这种强大的mRNA下调反应至关重要的一个信号是有效的RNA剪接。通过加强其剪接信号或去除其弱内含子，可以在较差的NMD底物上实现较强的mRNA下调。有效的剪接也强烈地促进了翻译，为增强的NMD提供了一个分子解释，并表明有效的剪接可能已经进化到增强蛋白质的产生和RNA的监视。我们的结果提出了一种简单的方法来增加表达载体中的蛋白质表达，并治疗由无义和移码突变引起的人类遗传病。
Aberrant mRNAs harboring premature termination codons (PTCs or nonsense codons) are degraded by the nonsense-mediated mRNA decay (NMD) pathway. mRNAs transcribed from genes that naturally acquire PTCs during lymphocyte development are strongly downregulated by PTCs. Here we show that a signal essential for this robust mRNA downregulatory response is efficient RNA splicing. Strong mRNA downregulation can be conferred on a poor NMD substrate by either strengthening its splicing signals or removing its weak introns. Efficient splicing also strongly promotes translation, providing a molecular explanation for enhanced NMD and suggesting that efficient splicing may have evolved to enhance both protein production and RNA surveillance. Our results suggest simple approaches for increasing protein expression from expression vectors and treating human genetic diseases caused by nonsense and frameshift mutations.