Exploring the Role of DNMT1 in RNA m⁵C Methylation (SLAM-seq)
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ABSTRACT:
PROVIDER: PRJNA1228132 | ENA |
REPOSITORIES: ENA
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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:Exploring the Role of DNMT1 in RNA m⁵C Methylation (RNA-BS-SEQ DNMT1 knockdown)
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Project description:Exploring the Role of DNMT1 in RNA m⁵C Methylation (eCLIPseq II)
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Project description:Exploring the Role of DNMT1 in RNA m⁵C Methylation (Ribo-seq)
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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: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 | 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 | GSE290472 | GEO
Project description:Exploring the Role of DNMT1 in RNA m⁵C Methylation (RNA-BS-SEQ NSUN2 Knock down)
| PRJNA1228128 | ENA
Project description:Despite considerable speculation for the role of cytosine (DNA) methylation in biological and molecular processes in insects, direct functional tests are lacking. Here we provide evidence for the functional role of the maintenance DNA methyltransferase 1 (Dnmt1) in an insect using experimental manipulation. Through RNA interference (RNAi) we successfully post-transcriptionally knocked down Dnmt1 in ovarian tissue of the hemipteran Oncopeltus fasciatus (the large milkweed bug). Individuals depleted for dnmt1, and subsequently DNA methylation, failed to reproduce. Manipulating the levels of DNA methylation did not result in changes in overall gene expression. Furthermore, reductions in levels of DNA methylation at transposable elements (TEs) did not lead to large-scale reactivation of TE transcription. Despite the lack of a causal relationship between reduced DNA methylation and gene expression in the tissue we surveyed, eggs were inviable revealing an important function of DNA methylation in O. fasciatus. Our work provides direct experimental evidence for a functional role of Dnmt1 and DNA methylation in insects and presents O. fasciatus as a tractable model for further exploration of the function of DNA methylation in other tissues and life history circumstances for insects.
2018-07-05 | GSE109199 | GEO