The late steps of plant nonsense-mediated mRNA decay
The late steps of plant nonsense-mediated mRNA decay
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DOI：
10.1111/tpj.12015
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发表时间：
2013-01-01
期刊：
影响因子：
7.2
通讯作者：
Silhavy, Daniel
中科院分区：
文献类型：
--
作者：
Merai, Zsuzsanna;Benkovics, Anna H.;Silhavy, Daniel
无意义介导的信使核糖核酸衰变(NMD)是一种真核质量控制系统，可以识别和降解含有提前终止密码子(PTCs)的mRNAs。如果翻译在PTC处终止，UPF1 NMD因子与终止的核糖体结合，并招募UPF2和UPF3形成功能性NMD复合体，从而触发含有PTC的转录本的快速衰退。虽然NMD缺乏症在植物中是致死的，但植物NMD的机制仍不清楚。为了了解NMD复合体的形成是如何导致转录衰退的，我们从功能上定位了UPF1和SMG7植物NMD因子，这两个因子可能是NMD靶标降解的关键角色。我们的数据表明，UPF1的富含半胱氨酸组氨酸(CH)和解旋酶结构域只在NMD的早期步骤中是必不可少的，而高度磷酸化的N-末端和C-末端在NMD的靶转录降解步骤中起着多余但必不可少的作用。我们还表明SMG7的N-末端和C-末端区域都是NMD所必需的。N端含有NMD早期步骤所需的磷酸丝氨酸结合域，而C端则需要触发NMD靶向转录本的降解。此外，SMG7是一个P小体成分，也可以将UPF1从细胞质重新动员到加工小体(P小体)中。我们认为，UPF1的N端和C端的磷酸化区域将SMG7招募到功能性的NMD复合体中，然后SMG7将含有PTC的转录本转运到P小体中进行降解。
Nonsense-mediated mRNA decay (NMD) is a eukaryotic quality control system that identifies and degrades mRNAs containing premature termination codons (PTCs). If translation terminates at a PTC, the UPF1 NMD factor binds the terminating ribosome and recruits UPF2 and UPF3 to form a functional NMD complex, which triggers the rapid decay of the PTC-containing transcript. Although NMD deficiency is seedling lethal in plants, the mechanism of plant NMD remains poorly understood. To understand how the formation of the NMD complex leads to transcript decay we functionally mapped the UPF1 and SMG7 plant NMD factors, the putative key players of NMD target degradation. Our data indicate that the cysteine-histidine-rich (CH) and helicase domains of UPF1 are only essential for the early steps of NMD, whereas the heavily phosphorylated N- and C-terminal regions play a redundant but essential role in the target transcript degradation steps of NMD. We also show that both the N-and the C-terminal regions of SMG7 are essential for NMD. The N terminus contains a phosphoserine-binding domain that is required for the early steps of NMD, whereas the C terminus is required to trigger the degradation of NMD target transcripts. Moreover, SMG7 is a P-body component that can also remobilize UPF1 from the cytoplasm into processing bodies (P bodies). We propose that the N-and C-terminal phosphorylated regions of UPF1 recruit SMG7 to the functional NMD complex, and then SMG7 transports the PTC-containing transcripts into P bodies for degradation.