The role of yeast m6A methyltransferase in peroxisomal fatty acid oxidation.

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 stationaryphase
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.