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无义介导的mRNA降解机制在不同生物界间的保守性

Inter-kingdom conservation of mechanism of nonsense-mediated mRNA decay.

作者信息

Kerényi Zoltán, Mérai Zsuzsanna, Hiripi László, Benkovics Anna, Gyula Péter, Lacomme Christophe, Barta Endre, Nagy Ferenc, Silhavy Dániel

机构信息

Agricultural Biotechnology Center, Gödöllo, Hungary.

出版信息

EMBO J. 2008 Jun 4;27(11):1585-95. doi: 10.1038/emboj.2008.88. Epub 2008 May 1.

Abstract

Nonsense-mediated mRNA decay (NMD) is a quality control system that degrades mRNAs containing premature termination codons. Although NMD is well characterized in yeast and mammals, plant NMD is poorly understood. We have undertaken the functional dissection of NMD pathways in plants. Using an approach that allows rapid identification of plant NMD trans factors, we demonstrated that two plant NMD pathways coexist, one eliminates mRNAs with long 3'UTRs, whereas a distinct pathway degrades mRNAs harbouring 3'UTR-located introns. We showed that UPF1, UPF2 and SMG-7 are involved in both plant NMD pathways, whereas Mago and Y14 are required only for intron-based NMD. The molecular mechanism of long 3'UTR-based plant NMD resembled yeast NMD, whereas the intron-based NMD was similar to mammalian NMD, suggesting that both pathways are evolutionarily conserved. Interestingly, the SMG-7 NMD component is targeted by NMD, suggesting that plant NMD is autoregulated. We propose that a complex, autoregulated NMD mechanism operated in stem eukaryotes, and that despite aspect of the mechanism being simplified in different lineages, feedback regulation was retained in all kingdoms.

摘要

无义介导的mRNA降解(NMD)是一种质量控制系统,可降解含有提前终止密码子的mRNA。尽管NMD在酵母和哺乳动物中已得到充分表征,但植物中的NMD却知之甚少。我们对植物中的NMD途径进行了功能剖析。通过一种能够快速鉴定植物NMD反式作用因子的方法,我们证明了植物中存在两种NMD途径,一种消除具有长3'UTR的mRNA,而另一种不同的途径则降解含有位于3'UTR的内含子的mRNA。我们表明,UPF1、UPF2和SMG-7参与了植物的两种NMD途径,而Mago和Y14仅为基于内含子的NMD所必需。基于长3'UTR的植物NMD的分子机制类似于酵母NMD,而基于内含子的NMD则类似于哺乳动物NMD,这表明这两种途径在进化上是保守的。有趣的是,SMG-7 NMD组分是NMD的作用靶点,这表明植物NMD是自动调节的。我们提出,一种复杂的、自动调节的NMD机制在真核生物主干中起作用,并且尽管该机制在不同谱系中有所简化,但反馈调节在所有生物界中都得以保留。

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