Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NSUN2 Facilitates Dicer Cleavage of DNA Damage-Associated R-Loops to Promote Repair [ONT direct RNA sequencing]

ABSTRACT: DNA integrity is constantly challenged by both endogenous and exogenous damaging agents, resulting in various forms of damage. Failure to repair DNA accurately leads to genomic instability, a hallmark of cancer. Distinct pathways exist to repair different types of DNA damage. Double-strand breaks (DSBs) represent particularly severe form of damage, due to physical separation of DNA strands. Repair of DSBs requires activity of RNA Polymerase II (RNAPII) and generation of Damage-associated transcripts (DARTs). Here we show that the RNA m5C-methyltransferase NSUN2 localizes to DSBs in transcription-dependent manner, where it binds to and methylates DARTs. Depletion of NSUN2 results in an accumulation of nascent DARTs around DSBs, specifically of the de novo primary DARTs. Furthermore, we detected an RNA-dependent interaction between NSUN2 and DICER, which was stimulated by DNA damage. NSUN2 activity promoted Dicer cleavage of DARTs associated R-loops, which is required for efficient DNA repair. We report a previously unrecognized role of the RNA m5C-methyltransferase NSUN2 within RNA-dependent DNA damage response, highlighting its function as a DICER chaperone for the clearance of non-canonical substrates such as DARTs, thereby contributing to genomic integrity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304944 | GEO | 2025/08/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage

Project description:The endonuclease Dicer is a key component of the human RNA interference (RNAi) pathway and known for its role in cytoplasmic micro RNA (miRNA) production. Recent findings suggest that non-canonical Dicer generates small non-coding RNA (ncRNA) to mediate the DNA damage response (DDR). Here we show that human Dicer is phosphorylated in the platform-PAZ-connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks (DSBs). We further demonstrate that turnover of damage-induced nuclear dsRNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes spontaneous DNA damage and delays DNA repair. Taken together, we place Dicer in context of the DDR by demonstrating DNA damage-inducible phospho-switch that causes localised processing of nuclear dsRNA by p-Dicer to promote DNA repair.

2018-12-08 | GSE75892 | GEO

Modified Y RNA-derived fragments form a complex with YBX1 and PARP1 to promote DNA repair

Project description:To protect genome integrity from pervasive threats of damage and prevent diseases like cancer, cells employ an integrated network of signalling pathways called the DNA damage response. These pathways involve both protein and RNA components which can act within the damaged cell or be transferred intercellularly to influence population-wide responses to damage. Here, we show that radioprotection can be conferred by damage-derived exosomes and is dependent on YBX1-packaged Y3-derived ysRNA. These ysRNA enter the nucleus of bystander cells upon DNA damage to become methylated by NSUN2. This allows interaction with YBX1 at double strand break (DSB) sites to promote efficient DNA repair and cell survival through complex formation with PARP1. YBX1 facilitates increased PARP1 auto-modification and ADP-ribosylation of ysRNA, promoting increased PARP1 residency at DSBs. We therefore highlight a new role for these under-studied species of small non-coding RNA in DNA repair.

2025-07-02 | GSE269346 | GEO

RNA expression and m5c modification in NSUN2 kncok down CaSki cell

Project description:5-methylcytosine (m5C) modification ubiquitously occurs on mammalian mRNAs and plays important roles in multiple biological processes. Currently, the role of m5C in cancer initiation and progression is gaining more and more research attention, but the detailed mechanism remains unclear. As an m5C methyltransferase with unique mRNA catalytic activity, NSUN2 was found to be highly expressed in multiple cancers including gastric, bladder, gallbladder, and breast cancers, suggesting NSUN2 might exert oncogenic properties through affecting m5C levels in cancer cells. Therefore, to understand the potential roles of RNA m5C modification in tumorigenesis of cervical cancer, we established NSUN2 stable knockdown CaSki cell, and perform RNA-seq and RNA-BisSeq to figure out the possible pathway involved in cervical cancer development.

2021-09-24 | GSE184621 | GEO

5-methylcytosine (m5C) RNA modification controls the innate immune response to virus infection by regulating type I interferons

Project description:Cytosine-5 methylation (m5C) is one of the most prevalent modifications of RNA, playing important roles in RNA metabolism, nuclear export, and translation. However, the potential role of RNA m5C methylation in innate immunity remains elusive. Here we show that depletion of NSUN2, an m5C methyltransferase, significantly inhibits the replication and gene expression of a wide range of RNA and DNA viruses. Notably, we found that this antiviral effect is largely driven by an enhanced type I interferon (IFN) response. The antiviral signaling pathway is dependent on the cytosolic RNA sensor RIG-I but not MDA5. Transcriptome-wide mapping of m5C following NSUN2 depletion in human A549 cells revealed a marked reduction in the m5C methylation of several abundant non-coding RNAs (ncRNAs). However, m5C methylation of viral RNA was not noticeably altered by NSUN2 depletion. In NSUN2-depleted cells, the host RNA polymerase (Pol) III transcribed ncRNAs, in particular RPPH1 and 7SL RNAs, were substantially upregulated, leading to an increased level in unshielded 7SL RNA in cytoplasm, which served as direct ligands for the RIG-I mediated IFN response. In NSUN2 depleted cells, inhibition of Pol III transcription or silencing of RPPH1 and 7SL RNA dampened IFN signaling, partially rescuing viral replication and gene expression. Finally, depletion of NSUN2 in an ex vivo human lung model and a mouse model inhibits viral replication and reduces pathogenesis which is accompanied by enhanced type I IFN responses. Collectively, our data demonstrate that RNA m5C methylation controls antiviral innate immunity through modulating m5C methylome of ncRNAs and their expression.

2022-09-26 | GSE174374 | GEO

Transcriptionally active chromatin channels DNA double-strand breaks to RAD51-dependent repair

Project description:Cells have developed effective mechanisms, namely homologous recombination (HR) and non-homologous end-joining (NHEJ), to repair DNA double-strand breaks (DSBs), which are considered to be the most deleterious type of damage that can challenge genome integrity. While these pathways coexist to repair DSBs, the mechanisms by which one of these pathways is chosen to repair a particular DSB remain unclear. Here, we show that the chromatin context in which a break occurs participates in this choice and that transcriptionnaly active chromatin channels repair to HR. By using a human cell line expressing a restriction enzyme fused to the ligand binding domain of the oestrogen receptor (AsiSI-ER)2,3, together with a genome wide chromatin immunoprecipitation-sequencing (ChIP-seq) approach, we establish that distinct DSBs induced across the genome are not necessarily repaired by the same pathway. Indeed, we identify an HR-prone subset of DSBs that recruit the HR protein RAD51, undergo resection, and rely on RAD51 for efficient repair. These DSBs are located in actively transcribed genes, and repair at such DSBs can be switched to RAD51-independent repair pathway upon transcriptional inhibition. Moreover, we show that HR is targeted to transcribed loci thanks to the elongation-associated H3K36me3 histone mark. Indeed depletion of HYPB, the main H3K36 tri methyltransferase severally impedes the use of HR at those DSBs. Our study, thereby demonstrates a clear role for chromatin in DSB repair pathway choice in human cells.

2014-03-23 | E-MTAB-1241 | biostudies-arrayexpress

Epitranscriptomic cytidine methylation of the Hepatitis B viral RNA encapsidation signal ensure the reverse transcription of viral RNA [PAR-CLIP]

Project description:Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of both cellular and viral RNAs. One prominent modification, the cytidine methylation 5-methylcytidine (m5C), is found on the RNA of HIV-1, where m5C enhances the translation and splicing of HIV-1 RNA. However, whether m5C functionally enhances the RNA of other pathogenic viruses remain elusive. Here, we report that the RNA of hepatitis B virus (HBV) is enriched with a high level of m5C, mediated mainly through the cellular methyltransferase NSUN2. Intrigingly, the most prominent cluster of NSUN2-deposited m5C is found on the epsilon hairpin, an RNA element required for viral RNA encapsidation and reverse transcription. Loss of m5C from HBV RNA due to depletion of NSUN2 resulted in a modest decrease in viral capsid protein (HBc) translation, yet this is accompaneied by a near-complete loss of the reverse transcribed viral DNA. Similarly, mutations introduced to remove the methylated cytidines resulted in a translation decrease and block of reverse transcription. Furthermore, pharmacological disruption of m5C deposition with a nucleoside analogue led to a significant decrease in HBV replication. Thus, our data indicates m5C methylations is a critical enhancer of the epsilon element in HBV reverse transcription. Our study suggests the theraputic potential of targeting the m5C methyltransfer process on the HBV 5’epsilon as an alternative antiviral stratagy.

2024-05-20 | GSE250108 | GEO

Epitranscriptomic cytidine methylation of the Hepatitis B viral RNA encapsidation signal ensure the reverse transcription of viral RNA [PA-m6A-seq]

2024-05-20 | GSE250107 | GEO

Epitranscriptomic cytidine methylation of the Hepatitis B viral RNA encapsidation signal ensure the reverse transcription of viral RNA [PA-m5C-seq 2]

2024-05-20 | GSE261877 | GEO

Epitranscriptomic cytidine methylation of the Hepatitis B viral RNA encapsidation signal ensure the reverse transcription of viral RNA [RNA-Seq]

2024-05-20 | GSE250105 | GEO

Epitranscriptomic cytidine methylation of the Hepatitis B viral RNA encapsidation signal ensure the reverse transcription of viral RNA [PA-m5C-seq]

2024-05-20 | GSE250106 | GEO