Exploring the Role of DNMT1 in RNA m⁵C Methylation (RNA-BS-SEQ NSUN2 Knock down)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1228128 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. However, point mutations in its RFTS domain lead to late-onset neurodegeneration such as the autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here we demonstrated that wild-type DNMT1 also has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When DNMT1 RFTS domain is mutated in the case of ADCA-DN disorder, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results highlight a novel role for DNMT1 in regulating both DNA and RNA methylation as well as mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.
2025-05-06 | GSE290472 | GEO
Project description:DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. However, point mutations in its RFTS domain lead to late-onset neurodegeneration such as the autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here we demonstrated that wild-type DNMT1 also has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When DNMT1 RFTS domain is mutated in the case of ADCA-DN disorder, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results highlight a novel role for DNMT1 in regulating both DNA and RNA methylation as well as mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.
2025-05-06 | GSE218053 | GEO
Project description:Exploring the Role of DNMT1 in RNA m⁵C Methylation (RNA-BS-SEQ DNMT1 knockdown)
| PRJNA901995 | ENA
Project description:DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. However, point mutations in its RFTS domain lead to late-onset neurodegeneration such as the autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here we demonstrated that wild-type DNMT1 also has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When DNMT1 RFTS domain is mutated in the case of ADCA-DN disorder, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results highlight a novel role for DNMT1 in regulating both DNA and RNA methylation as well as mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.
2025-05-06 | GSE290473 | GEO
Project description:DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. However, point mutations in its RFTS domain lead to late-onset neurodegeneration such as the autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here we demonstrated that wild-type DNMT1 also has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When DNMT1 RFTS domain is mutated in the case of ADCA-DN disorder, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results highlight a novel role for DNMT1 in regulating both DNA and RNA methylation as well as mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.
2025-05-06 | GSE290508 | GEO
Project description:DNA methyltransferase 1 (DNMT1) is an enzyme known for DNA methylation maintenance. However, point mutations in its RFTS domain lead to late-onset neurodegeneration such as the autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) disorder. Here we demonstrated that wild-type DNMT1 also has the capability to bind to mRNA transcripts and facilitate 5-methylcytosine (m5C) RNA methylation by recruiting NOP2/Sun RNA methyltransferase 2 (NSUN2). RNA m5C methylation, in turn, promotes RNA stability for those genes modulating mitochondrial function. When DNMT1 RFTS domain is mutated in the case of ADCA-DN disorder, it triggers aberrant DNMT1-RNA interaction and significantly elevated m5C RNA methylation and RNA stability for a portion of metabolic genes. Consequently, increased levels of metabolic RNA transcripts contribute to cumulative oxidative stress, mitochondrial dysfunction, and neurological symptoms. Collectively, our results highlight a novel role for DNMT1 in regulating both DNA and RNA methylation as well as mitochondrial function, shedding light on the pathogenic mechanism of DNMT1 mutation-induced neurodegeneration.
2025-05-06 | GSE290474 | GEO
Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (RNA-BS-seq)
| PRJNA784446 | ENA
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
Project description:A Dominant mutation in Dnmt1 leads epigenetic changes (RNA-BS-seq Mouse Cortex)
| PRJNA901993 | ENA
Project description:Autosomal-recessive loss of the NSUN2 gene has been recently identified as a causative link to intellectual disability disorders in humans. NSun2 is an RNA methyltransferase modifying cytosine-5 in transfer RNAs (tRNA). Whether NSun2 methylates additional RNA species is currently debated. Here, we adapted the individual-nucleotide resolution UV cross-linking and immunoprecipitation method (iCLIP) to identify NSun2-mediated methylation in RNA transcriptome. We confirm site-specific methylation in tRNA and identify messenger and non-coding RNAs as potential methylation targets for NSun2. Using RNA bisulfite sequencing we establish Vault non-coding RNAs as novel substrates for NSun2 and identified six cytosine-5 methylated sites. Furthermore, we show that loss of cytosine-5 methylation in Vault RNAs causes aberrant processing into argonaute-associating small RNA fragments (svRNA). Thus, impaired Vault non-coding RNA processing may be an important contributor to the etiology of NSUN2-deficieny human disorders. mRNA-seq in Embryonic kidney (HEK293) cells transfected with siRNA against Nsun2 vs control
2013-07-23 | E-GEOD-44384 | biostudies-arrayexpress