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M6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [MeRIP-seq]

ABSTRACT: m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [MeRIP-seq]

PROVIDER: PRJNA595543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10690131_1.fastq.gz	Fastqsanger.gz
	SRR10690131_2.fastq.gz	Fastqsanger.gz
	SRR10690132_1.fastq.gz	Fastqsanger.gz
	SRR10690132_2.fastq.gz	Fastqsanger.gz
	SRR10690133_1.fastq.gz	Fastqsanger.gz

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m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [MeRIP-seq]

Project description:Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex (MTC) that catalyzes mRNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent function of the MTC, m6A independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 drives senescence-associated secretory phenotype (SASP) in a m6A-independent manner. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL14 is redistributed to the enhancers, while METTL3 is localized to the pre-existing NF-B sites within the promoters of the SASP genes during senescence. METTL3 interacts with NF-B and they are mutually dependent on their associations with the promoters of SASP genes. METTL14 but not METTL3 is necessary for function of SASP gene enhancers. METTL3 and METTL14 are required for both the tumor-promoting and immune surveillance functions of senescent cells mediated by SASP in vivo in mouse models. In summary, our results report a m6A independent function of the METTL3 and METTL14 complex in promoting SASP through regulating transcription by genome-wide redistribution of METTL14 to enhancers and METTL3 to promoters of SASP genes during senescence.

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m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype

Project description:m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype

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m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [rna.M3]

Project description:m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [rna.M3]

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Determine the methyltransferase activities of METTL3, METTL14, and METTL16 via MeRIP-seq (m6A-seq)

Project description:All the three enzymes, METTL3, METTL14, and METTL16, belong to methyltransferase like (METTL) family and possess the ability to deposit N6-methyladenosine (m6A) in mRNA. Via immunofluorescence staining and wertern blotting, we discovered either METTL3 or METTL14 mainly localize in nuclear, but METTL16 localizes in both cytosol and nuclei. To compare the m6A methyltransferase activities of the three m6A 'writers' and better understand their differences, MeRIP-seq (m6A-seq) was conducted with poly(A) RNAs isolaed from HEK293T cells with METTL3, 14 and 16 knockout.

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m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [ChIP-seq]

Project description:m6A independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype [ChIP-seq]

| PRJNA595544 | ENA