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5' UTR-dependent m6A methylation regulates aging and circadian rhythms in Drosophila

ABSTRACT: 5' UTR-dependent m6A methylation regulates aging and circadian rhythms in Drosophila

PROVIDER: PRJNA810079 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18134927_1.fastq.gz	Fastqsanger.gz
	SRR18134927_2.fastq.gz	Fastqsanger.gz
	SRR18134928_1.fastq.gz	Fastqsanger.gz
	SRR18134928_2.fastq.gz	Fastqsanger.gz
	SRR18134929_1.fastq.gz	Fastqsanger.gz

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5' UTR-dependent m6A methylation regulates aging and circadian rhythms in Drosophila [RNA-seq head]

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Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation [siMettl3]

Project description:Circadian transcriptional rhythms are necessary for lipid metabolic homeostasis. Disruptions can lead to metabolic diseases. Whether epigenetic N6-methyladenosine (m6A) mRNA methylation impacts circadian regulation of lipid metabolism is unclear. Here, we show m6A mRNA methylation oscillations in murine liver depend upon a functional circadian clock. Hepatic deletion of Bmal1 increased m6A mRNA methylation, particularly of PPaRα. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreased PPaRα m6A abundance and increased PPaRα mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. Our data suggest YTH domain family 2 (YTHDF2, a m6A binding protein) binds to PPaRα, prolonging its lifetime and mRNA expression. Reactive oxygen species accumulation increased PPaRα transcript m6A levels, revealing a possible mechanism for circadian clock disruption on m6A mRNA methylation. These data suggest m6A RNA methylation is important for circadian clock regulation of downstream genes and lipid metabolism that impacts metabolic outcome.

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