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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [CLIP-seq]

ABSTRACT: Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [CLIP-seq]

PROVIDER: PRJNA1039792 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26815934_1.fastq.gz	Fastqsanger.gz
	SRR26815934_2.fastq.gz	Fastqsanger.gz
	SRR26815935_1.fastq.gz	Fastqsanger.gz
	SRR26815935_2.fastq.gz	Fastqsanger.gz
	SRR26815936_1.fastq.gz	Fastqsanger.gz

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [CLIP-seq]

Project description:RNA modifications, including m6A, critically modulate protein expression program in a range of cellular processes. Although cellular senescence has been linked to age-related diseases and functional declines, the landscape and impact of m6A modification are poorly understood. Here, we report a robust m6A modification of Patched-Domain Containing Protein 4 (PTCHD4) mRNA at m6A in senescent cells. The METTL3/METTL14 complex was found to mediate the m6A modification of PTCHD4 mRNA, which increased PTCHD4 mRNA stability and PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as being responsible for stabilization and increased abundance of PTCHD4 mRNA by m6A modification. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells, and sensitized them to senolytic treatments and apoptosis. Our results support the notion that m6A modifications critically control senescence programs, and that factors such as METTL3/METTL14 and IGF2BP1, implicated in PTCHD4 mRNA m6A metabolism, could be exploited to eliminate senescent cells for therapeutic benefit.

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [array]

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [RNA-seq]

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival

Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [array]

Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [array]

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [RNA-seq]

Project description:Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival [RNA-seq]

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent cell survival.

Project description:RNA modifications, including N6-methyladenosine (m6A), critically modulate protein expression programs in a range of cellular processes. Although the transcriptomes of cells undergoing senescence are strongly regulated, the landscape and impact of m6A modifications during senescence are poorly understood. Here, we report a robust m6A modification of PTCHD4 mRNA, encoding Patched Domain-Containing Protein 4, in senescent cells. The METTL3/METTL14 complex was found to incorporate the m6A modification on PTCHD4 mRNA; addition of m6A rendered PTCHD4 mRNA more stable and increased PTCHD4 production. MeRIP RT-qPCR and eCLIP analyses were used to map this m6A modification to the last exon of PTCHD4 mRNA. Further investigation identified IGF2BP1, but not other m6A readers, as responsible for the stabilization and increased abundance of m6A-modified PTCHD4 mRNA. Silencing PTCHD4, a transmembrane protein, enhanced growth arrest and DNA damage in pre-senescent cells and sensitized them to senolysis and apoptosis. Our results indicate that m6A modification of PTCHD4 mRNA increases the production of PTCHD4, a protein associated with senescent cell survival, supporting the notion that regulating m6A modification on specific mRNAs could be exploited to eliminate senescent cells for therapeutic benefit.

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Increased PTCHD4 expression via m6A modification of PTCHD4 mRNA promotes senescent-cell survival

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-17 | GSE247621 | GEO

Senescent cells cluster CTCF on nuclear speckles to sustain their splicing program [e-CLIP]

Project description:Senescent cells cluster CTCF on nuclear speckles to sustain their splicing program [e-CLIP]

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Project description:m6A and YTHDF1, YTHDF2, YTHDF3 mapping of IAV RNA with PAR-CLIP and pA-m6A-seq

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