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酵母中的mA甲基转移酶Ime4与线粒体功能

The mA methyltransferase Ime4 and mitochondrial functions in yeast.

作者信息

Yadav Pradeep Kumar, Rajasekharan Ram

机构信息

Lipidomic Centre, Department of Lipid Science, CSIR-Central Food Technological Research Institute (CFTRI), Mysore, Karnataka, 570020, India.

Academy of Scientific and Innovative Research, CSIR-CFTRI, Mysore, India.

出版信息

Curr Genet. 2018 Apr;64(2):353-357. doi: 10.1007/s00294-017-0758-8. Epub 2017 Oct 3.

Abstract

In eukaryotes, the precise transcriptional and post-transcriptional regulations of gene expression are crucial for the developmental processes. More than 100 types of post-transcriptional RNA modifications have been identified in eukaryotes. The deposition of N-methyladenosine (mA) into mRNA is among the most common post-transcriptional RNA modifications known in eukaryotes. It has been reported that mA RNA modification can regulate gene expression. The role of yeast mA methyltransferase (Ime4) in meiosis and sporulation in diploid cells is very well proven, but its physiological role in haploid cells has remained unknown until recently. Previously, we have shown that Ime4 epitranscriptionally regulates triacylglycerol (TAG) metabolism and vacuolar morphology in haploid cells. Mitochondrial dysfunction leads to TAG accumulation as lipid droplets (LDs) in the cells; besides, LDs are physically connected to the mitochondria. As of now there are no reports on the role of Ime4 in mitochondrial biology. Here we report the important role played by Ime4 in the mitochondrial morphology and functions in Saccharomyces cerevisiae. The confocal microscopic analysis showed that IME4 gene deletion causes mitochondrial fragmentation; besides, the ime4Δ cells showed a significant decrease in cytochrome c oxidase and citrate synthase activities compared to the wild-type cells. IME4 gene deletion causes mitochondrial dysfunction, and it will be interesting to find out the target genes of Ime4 related to the mitochondrial biology. The determination of the role of Ime4 and its targets in mitochondrial biology could probably help in formulating potential cures for the mitochondria-linked rare genetic disorders.

摘要

在真核生物中,基因表达精确的转录和转录后调控对于发育过程至关重要。真核生物中已鉴定出100多种转录后RNA修饰。N-甲基腺苷(mA)在mRNA中的沉积是真核生物中已知的最常见的转录后RNA修饰之一。据报道,mA RNA修饰可调控基因表达。酵母mA甲基转移酶(Ime4)在二倍体细胞减数分裂和孢子形成中的作用已得到充分证实,但直到最近其在单倍体细胞中的生理作用仍不清楚。此前,我们已经表明Ime4在转录后水平上调控单倍体细胞中的三酰甘油(TAG)代谢和液泡形态。线粒体功能障碍导致TAG以脂滴(LDs)的形式在细胞中积累;此外,脂滴与线粒体在物理上相连。截至目前,尚无关于Ime4在线粒体生物学中作用的报道。在此我们报告Ime4在酿酒酵母线粒体形态和功能中发挥的重要作用。共聚焦显微镜分析表明,IME4基因缺失导致线粒体碎片化;此外,与野生型细胞相比,ime4Δ细胞的细胞色素c氧化酶和柠檬酸合酶活性显著降低。IME4基因缺失导致线粒体功能障碍,找出与线粒体生物学相关的Ime4的靶基因将很有趣。确定Ime4及其靶标在线粒体生物学中的作用可能有助于制定针对线粒体相关罕见遗传病的潜在治疗方法。

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