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M6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells

ABSTRACT: m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells

PROVIDER: PRJNA962900 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24339403_1.fastq.gz	Fastqsanger.gz
	SRR24339403_2.fastq.gz	Fastqsanger.gz
	SRR24339404_1.fastq.gz	Fastqsanger.gz
	SRR24339404_2.fastq.gz	Fastqsanger.gz
	SRR24339405_1.fastq.gz	Fastqsanger.gz

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CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [CHIP-seq]

Project description:Maintaining centromere integrity is crucial for genome stability and proper chromosome segregation during mitosis. CENPA, a conserved histone H3 variant, is localized at the centromeres and plays an essential role in preserving centromere integrity and function. However, the mechanisms that retain CENPA at centromeres remain an enigma. In this study, we identified CENPA as an m6A reader of centromeric RNA (cenRNA), which is essential for its centromeric localization and function in maintaining centromere stability. We discovered a higher level of m6A modification on cenRNA in cancerous cells compared to normal cells. CENPA preferentially binds the cenRNAs with m6A modification, which stabilizes its localization in centromeric regions during the S phase of the cell cycle. We then identified two residues in CENPA responsible for m6A recognition. Mutations in these CENPA residues or removal of m6A on cenRNAs leads to the loss of centromere-bound CENPA during the S phase, thereby resulting in abnormal chromosome separation during mitosis and increased genomic instability. Consequently, this impairment in centromere integrity hindered cancer cell proliferation and tumor growth. Our findings unveiled a novel m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potentially new targets for cancer therapy.

2024-09-24 | GSE230879 | GEO

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [MeRIP-seq]

2024-09-24 | GSE230877 | GEO

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [RIP-Seq]

2024-09-24 | GSE247873 | GEO

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [ChIRP-seq]

2024-09-24 | GSE247871 | GEO

m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells

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

2024-09-24 | GSE230880 | GEO

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [RIP-Seq]

Project description:CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [RIP-Seq]

| PRJNA1040850 | ENA

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [MeRIP-seq]

Project description:CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [MeRIP-seq]

| PRJNA962902 | ENA

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [ChIRP-seq]

Project description:CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [ChIRP-seq]

| PRJNA1040847 | ENA

CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [CHIP-seq]

Project description:CENPA as a reader of m6A-modified centromeric RNA to ensure centromere integrity in cancer cells [CHIP-seq]

| PRJNA962903 | ENA

Transcriptional Profiling of CENPA-Depleted Prostate Cancer Cell Lines

Project description:Overexpression of centromeric proteins has been identified in a number of human malignancies, though their functional and mechanistic contributions to disease progression have not been characterized. CENPA, the centromeric histone H3 variant, is the epigenetic mark that determines centromere identity. Here, we demonstrate that CENPA is highly overexpressed in prostate cancer in both tissue and cell lines, and the level of CENPA expression correlates with the stage of disease. Gain-of- and loss-of-function experimentation confirms that CENPA promotes prostate cancer cell line growth. Integrated sequencing studies further reveal a previously unidentified function of CENPA as a transcriptional regulator that modulates expression of critical proliferation, cell-cycle, and centromere/kinetochore genes. Our findings, therefore, suggest a previously undescribed biological function for CENPA, a protein normally thought to be solely and importantly involved in centromere identity.

2019-03-06 | GSE127836 | GEO

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