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M6A methylation regulates the fate of endogenous retrovirus transcripts [CUT & RUN]

ABSTRACT: m6A methylation regulates the fate of endogenous retrovirus transcripts [CUT & RUN]

PROVIDER: PRJNA656303 | ENA |

REPOSITORIES: ENA

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m6A methylation regulates the fate of endogenous retrovirus transcripts [CUT & RUN]

Project description:Using a genome-scale CRISPR knockout screening in mouse embryonic stem cells, we identify m6A RNA methylation as an important regulatory component that restricts the activity of endogenous retroviruses of the IAP (intracisternal A-particles) family. The m6A methylation of IAP mRNAs occurs on their 5’ end, is catalyzed by the complex of methyltransferase-like (METTL)3/METTL14 proteins whose depletion, along with other complex subunits, namely WTAP and ZC3H13, leads to increased IAP transcript abundance. Using auxin-dependent degron, we show that rapid removal of METTL3, METTL14 and ZC3H13 further increases IAP RNA abundance in a progressive and reversible fashion. Finally, we demonstrate that m6A RNA reduces the stability of IAP transcripts

2020-08-11 | GSE156007 | GEO

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m6A methylation regulates the fate of endogenous retrovirus transcripts [CRISPR/Cas9]

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An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140 [CUT&RUN]

Project description:Speckled Protein 140 (SP140) is a chromatin reader with critical roles regulating immune cell transcriptional programs, and SP140 splice variants are associated with immune diseases including Crohn’s disease, multiple sclerosis, and chronic lymphocytic leukemia. SP140 expression is currently thought to be restricted to immune cells. However, by analyzing human transcriptomic datasets from a wide range of normal and cancer cell types, we found recurrent cancer-specific expression of SP140, driven by an alternative intronic promoter derived from an intronic endogenous retrovirus (ERV). The ERV belongs to the primate-specific LTR8B family. The ERV drives expression of multiple cancer-specific isoforms, including a nearly full-length isoform that retains all the functional domains of the full-length canonical isoform and is also localized within the nucleus, consistent with a role in chromatin regulation. In a fibrosarcoma cell line, silencing the cancer-specific ERV promoter of SP140 resulted in increased sensitivity to interferon-mediated cytotoxicity and dysregulation of multiple genes. Our findings implicate aberrant ERV-mediated SP140 expression as a novel mechanism contributing to immune gene dysregulation in a wide range of cancer cells.

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CUT&RUN HUDEP1 OE SOX6-Flag

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