The loss of SMG1 causes defects in quality control pathways in Physcomitrella patens.
The loss of SMG1 causes defects in quality control pathways in Physcomitrella patens.
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DOI：
10.1093/nar/gky225
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发表时间：
2018-06-20
影响因子：
14.9
通讯作者：
Davies B
中科院分区：
文献类型：
--
作者：
Lloyd JPB;Lang D;Zimmer AD;Causier B;Reski R;Davies B
无义介导的mRNA衰变（NMD）对真核生物RNA质量控制和基因调控具有重要意义。NMD以异常转录本为目标进行衰变，并直接影响非异常转录本的丰度。在动物中，SMG1激酶通过磷酸化核心NMD因子UPF1在NMD中发挥重要作用。尽管SMG1在植物界普遍存在，但对其功能知之甚少，可能是因为模式植物拟南芥的基因组中不存在SMG1。通过将我们之前在苔藓中建立的SMG1敲除与转录组分析相结合，我们揭示了植物中涉及SMG1的一系列过程。机器学习辅助分析表明，32%的多异构体基因产生NMD靶向转录本，并且停止密码子下游的剪接是NMD靶向的主要决定因素。此外，我们认为SMG1除了在mRNA质量控制中发挥作用外，还参与其他质量控制途径，影响DNA修复和未折叠蛋白反应。与此一致的是，smg1植物对DNA损伤的易感性增加，但对未折叠蛋白诱导剂的耐受性增加。SMG1在RNA、DNA和蛋白质质量控制中的潜在参与对植物中这些过程的研究具有重要意义。
Nonsense-mediated mRNA decay (NMD) is important for RNA quality control and gene regulation in eukaryotes. NMD targets aberrant transcripts for decay and also directly influences the abundance of non-aberrant transcripts. In animals, the SMG1 kinase plays an essential role in NMD by phosphorylating the core NMD factor UPF1. Despite SMG1 being ubiquitous throughout the plant kingdom, little is known about its function, probably because SMG1 is atypically absent from the genome of the model plant, Arabidopsis thaliana. By combining our previously established SMG1 knockout in moss with transcriptome-wide analysis, we reveal the range of processes involving SMG1 in plants. Machine learning assisted analysis suggests that 32% of multi-isoform genes produce NMD-targeted transcripts and that splice junctions downstream of a stop codon act as the major determinant of NMD targeting. Furthermore, we suggest that SMG1 is involved in other quality control pathways, affecting DNA repair and the unfolded protein response, in addition to its role in mRNA quality control. Consistent with this, smg1 plants have increased susceptibility to DNA damage, but increased tolerance to unfolded protein inducing agents. The potential involvement of SMG1 in RNA, DNA and protein quality control has major implications for the study of these processes in plants.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
64.5
作者：
Hogg JR;Goff SP
通讯作者：
Goff SP
影响因子：
28.2
作者：
Chen J;Crutchley J;Zhang D;Owzar K;Kastan MB
通讯作者：
Kastan MB
影响因子：
4.6
作者：
Causier B;Li Z;De Smet R;Lloyd JPB;Van de Peer Y;Davies B
通讯作者：
Davies B