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The m6A methyltransferase Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology in haploid yeast cells.

Pradeep Kumar, Yadav and Ram, Rajasekharan (2017) The m6A methyltransferase Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology in haploid yeast cells. Journal of Biological Chemistry, 292 (33). pp. 13727-13744.

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Abstract

N6-Methyladenosine (m6A) is among the most common modifications in eukaryotic mRNA. The role of yeast m6A methyltransferase, Ime4, in meiosis and sporulation in diploid strains is very well studied, but its role in haploid strains has remained unknown. Here, with the help of an immunoblotting strategy and Ime4-GFP protein localization studies, we establish the physiological role of Ime4 in haploid cells.Ourdata showed that Ime4 epitranscriptionally regulates triacylglycerol metabolism and vacuolar morphology through the long-chain fatty acyl-CoA synthetase Faa1, independently of the RNA methylation complex (MIS complex). The MIS complex consists of the Ime4, Mum2, and Slz1 proteins. Our affinity enrichment strategy (methylated RNA immunoprecipitation assays) using m6A polyclonal antibodies coupled with mRNA isolation, quantitative real-timePCR,andstandardPCRanalyses confirmed the presence ofm6A-modified FAA1 transcripts in haploid yeast cells. The term “epitranscriptional regulation” encompasses theRNAmodification-mediated regulation of genes. Moreover,we demonstrate that the Aft2 transcription factor up-regulates FAA1 expression. Because them6Amethylation machinery is fundamentally conserved throughout eukaryotes, our findings will help advance the rapidly emerging field ofRNAepitranscriptomics.The metabolic link identified here betweenm6A methylation and triacylglycerol metabolism via the Ime4 protein provides new insights into lipid metabolism and the pathophysiology of lipid-related metabolic disorders, such as obesity. Because the yeast vacuole isan analogue of the mammalian lysosome, our findings pave the way to better understand the role ofm6Amethylation in lysosome-related functions and diseases.

Item Type: Article
Uncontrolled Keywords: m6A methylation, triacylglycerol metabolism, Ime4 protein
Subjects: 500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 11 Lipid Biochemistry
600 Technology > 08 Food technology > 29 Microbiological food > 04 Yeast
Divisions: Dept. of Lipid Science
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 07 Feb 2019 04:06
Last Modified: 07 Feb 2019 04:06
URI: http://ir.cftri.com/id/eprint/13934

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