Centre for Plant Sciences, Faculty of Biological Sciences, University of Leeds, UK.
Plant Biotechnology, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Nucleic Acids Res. 2018 Jun 20;46(11):5822-5836. doi: 10.1093/nar/gky225.
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.
无意义介导的 mRNA 降解(NMD)在真核生物的 RNA 质量控制和基因调控中非常重要。NMD 靶向异常转录本进行降解,同时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 在整个植物界中普遍存在,但对其功能知之甚少,这可能是因为模型植物拟南芥的基因组中缺少 SMG1。通过将我们之前在苔藓中建立的 SMG1 敲除与转录组范围分析相结合,我们揭示了 SMG1 在植物中涉及的一系列过程。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,并且终止密码子下游的剪接接头是 NMD 靶向的主要决定因素。此外,我们还表明,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 损伤的敏感性增加,但对诱导未折叠蛋白的试剂的耐受性增加。SMG1 可能参与 RNA、DNA 和蛋白质的质量控制,这对研究这些过程在植物中的作用具有重要意义。