The m6A methyltransferase Ime4 and mitochondrial functions in yeast

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.

Epigenetic regulation of N6‐methyladenosine modifications in obesity

“…They showed that Ime4, yeast m6A methyltransferase, epi‐transcriptionally regulates triacylglycerol metabolism through the long‐chain fatty acyl‐CoA synthetase 71 . Another study also carried out by Yadav et al 72 . found that IME4 gene loss caused mitochondrial malfunction.…”

The interplay between m6A RNA methylation and noncoding RNA in cancer

“…The genome-wide distribution of n6-methyladenosine (m6A) was unclear until 2012, but m6A is the most common RNA modification of mRNAs. It is enriched in many eukaryotic species of mammals, plants, and yeast [1][2][3][4][5][6][7][8] and is found in prokaryotes, including bacteria and mycoplasma [9,10]. The mRNAs of 7676 mammalian genes were found to be modified by m6A [11].…”

Biological functions of m6A methyltransferases

“…2a). In addition to its direct effect on regulating triacylglycerol (TAG) metabolism in haploid cells, IME4 deletion caused mitochondrial fragmentation and dysfunction, which indirectly influenced TAG metabolism [65] (Fig. 2a).…”