Conservation of Nonsense-Mediated mRNA Decay Complex Components Throughout Eukaryotic Evolution.
Conservation of Nonsense-Mediated mRNA Decay Complex Components Throughout Eukaryotic Evolution.
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DOI：
10.1038/s41598-017-16942-w
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发表时间：
2017-11-30
影响因子：
4.6
通讯作者：
Davies B
中科院分区：
文献类型：
--
作者：
Causier B;Li Z;De Smet R;Lloyd JPB;Van de Peer Y;Davies B
无义介导的 mRNA 衰减 (NMD) 是调节转录质量和丰度的重要真核过程，并参与包括大脑发育和植物防御在内的多种过程。尽管一些 NMD 机制在各个王国之间得到了保留，但对其演变却知之甚少。核心 NMD 成分 UPF1 的磷酸化对于 NMD 至关重要，并且在哺乳动物中受到 SURF 复合物（UPF1、SMG1 激酶、SMG8、SMG9 和真核释放因子）的调节。然而，由于据报道真菌和植物拟南芥的基因组中SMG1缺失，因此目前尚不清楚UPF1如何在后生动物外被激活。我们使用比较基因组学来确定 NMD 途径在真核进化过程中的保守性。我们发现SURF成分存在于包括真菌在内的所有主要真核生物谱系中，这表明除了UPF1和SMG1之外，SMG8和SMG9也存在于18亿年前的最后一个真核共同祖先中。然而，尽管 SURF 复合体起源古老，我们还发现 SURF 因子在真核生物中独立丢失，这表明 NMD 重要途径内存在遗传缓冲。我们推断 SURF 在调节 UPF1 中发挥着古老的作用，以及未被发现的 NMD 调节途径的有趣可能性。
Nonsense-mediated mRNA decay (NMD) is an essential eukaryotic process regulating transcript quality and abundance, and is involved in diverse processes including brain development and plant defenses. Although some of the NMD machinery is conserved between kingdoms, little is known about its evolution. Phosphorylation of the core NMD component UPF1 is critical for NMD and is regulated in mammals by the SURF complex (UPF1, SMG1 kinase, SMG8, SMG9 and eukaryotic release factors). However, since SMG1 is reportedly missing from the genomes of fungi and the plant Arabidopsis thaliana, it remains unclear how UPF1 is activated outside the metazoa. We used comparative genomics to determine the conservation of the NMD pathway across eukaryotic evolution. We show that SURF components are present in all major eukaryotic lineages, including fungi, suggesting that in addition to UPF1 and SMG1, SMG8 and SMG9 also existed in the last eukaryotic common ancestor, 1.8 billion years ago. However, despite the ancient origins of the SURF complex, we also found that SURF factors have been independently lost across the Eukarya, pointing to genetic buffering within the essential NMD pathway. We infer an ancient role for SURF in regulating UPF1, and the intriguing possibility of undiscovered NMD regulatory pathways.
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