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The role of yeast m6A methyltransferase in peroxisomal fatty acid oxidation

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Abstract

The precise and controlled regulation of gene expression at transcriptional and post-transcriptional levels is crucial for the eukaryotic cell survival and functions. In eukaryotes, more than 100 types of post-transcriptional RNA modifications have been identified. The N6-methyladenosine (m6A) modification in mRNA is among the most common post-transcriptional RNA modifications known in eukaryotic organisms, and the m6A RNA modification can regulate gene expression. The role of yeast m6A methyltransferase (Ime4) in meiosis, sporulation, triacylglycerol metabolism, vacuolar morphology, and mitochondrial functions has been reported. Stress triggers triacylglycerol accumulation as lipid droplets. Lipid droplets are physically connected to the different organelles such as endoplasmic reticulum, mitochondria, and peroxisomes. However, the physiological relevance of these physical interactions remains poorly understood. In yeast, peroxisome is the sole site of fatty acid β-oxidation. The metabolic status of the cell readily governs the number and physiological function of peroxisomes. Under low-glucose or stationary-phase conditions, peroxisome biogenesis and proliferation increase in the cells. Therefore, we hypothesized a possible role of Ime4 in the peroxisomal functions. There is no report on the role of Ime4 in peroxisomal biology. Here, we report that IME4 gene deletion causes peroxisomal dysfunction under stationary-phase conditions in Saccharomyces cerevisiae; besides, the ime4Δ cells showed a significant decrease in the expression of the key genes involved in peroxisomal β-oxidation compared to the wild-type cells. Therefore, identification and determination of the target genes of Ime4 that are directly involved in the peroxisomal biogenesis, morphology, and functions will pave the way to better understand the role of m6A methylation in peroxisomal biology.

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Acknowledgements

This work was supported by the Council of Scientific and Industrial Research (CSIR), New Delhi. The corresponding author is a recipient of the JC Bose National Fellowship. We are thankful to Professor Jeffrey E. Gerst, Department of Molecular Genetics, Weizmann Institute of Science, Israel for providing the pUG36-RFP-PTS1 construct. We are grateful to the Department of Biochemistry of the Indian Institute of Science in Bangalore for the use of their facility for the radioactive study.

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RR conceived and initiated the project. RR, PKY, and PKR designed the experiments. PKY and PKR executed the experiments and analyzed the data. PKY, PKR, and RR discussed the data and wrote the paper.

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Correspondence to Ram Rajasekharan.

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The authors declare that they have no conflicts of interest.

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Communicated by M. Kupiec.

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Yadav, P.K., Rajvanshi, P.K. & Rajasekharan, R. The role of yeast m6A methyltransferase in peroxisomal fatty acid oxidation. Curr Genet 64, 417–422 (2018). https://doi.org/10.1007/s00294-017-0769-5

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  • DOI: https://doi.org/10.1007/s00294-017-0769-5

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