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Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNA Biogenesis

ABSTRACT: Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNA Biogenesis

PROVIDER: PRJNA776016 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16617180_1.fastq.gz	Fastqsanger.gz
	SRR16617180_2.fastq.gz	Fastqsanger.gz
	SRR16617181_1.fastq.gz	Fastqsanger.gz
	SRR16617181_2.fastq.gz	Fastqsanger.gz
	SRR16617182_1.fastq.gz	Fastqsanger.gz

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Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNA Biogenesis

Project description:N6-methyladenosine (m6A) regulates various aspects of RNA biology. Although m6A methylation on mRNA has been shown to be co-transcriptionally deposited, a possible regulatory role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) components are co-localized to many promoters and enhancers and deposit the m6A modification to local chromatin associated transcripts including pre-mRNAs, promoter upstream transcripts (PROMPTs) and enhancer RNAs (eRNAs), suggesting a possible regulatory role for m6A methylation at these transcripts. Indeed, PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3 depleted cells. The Integrator complex has been reported to cleave nascent RNAs, which causes transcriptional attenuation. Importantly, simultaneous depletion of METTL3 and INTS11, the endonuclease subunit in the Integrator complex, suppressed the nascent RNA decrease, suggesting an antagonistic relationship between METTL3 and the Integrator complex. Consistently, we found an elevated level of INTS11 at promoters and enhancers upon loss of MTC or the m6A binder HnRNP G. Taken together, our findings suggest that MTC-mediated m6A modification protects nascent RNAs and promotes productive transcription, thus unraveling a novel layer of gene regulation imposed by RNA m6A modification.

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Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNAs Stability [MeRIP]

Project description:N6-methyladenosine (m6A) has been shown to regulate various aspects of mRNA biology. Although m6A has been shown to be co-transcriptionally deposited in mRNA by the chromatin-bound methyltranferase METTL3, the precise role of METTL3 and the resulting m6A methylation remain incompletely understood. Here, we demonstrate that the nascent RNAs generated from enhancers and promoters are co-transcriptionally and dynamically regulated by the chromatin bound METTL3/14 methyltransferase complex, and the demethylase, ALKBH5. Importantly, nascent RNA m6A is recognized by the reader protein hnRNP G, which prevents access of the RNA endonuclease INTS11 and thus protects nascent RNA from inappropriate degradation. Our study thus reveals an important chromatin function of m6A in stabilizing the enhancer- and promoter-derived nascent RNAs, which function to promote transcription activation.

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Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNAs Stability

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Dynamic Control of Chromatin-associated m6A Methylation Regulates Nascent RNAs Stability [PRO-seq]

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