The m6A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE194100 | GEO | 2022/01/23
REPOSITORIES: GEO
Similar Datasets
Project description:The m6A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay
| PRJNA799056 | ENA
Project description:The N6-methyladenosine (m6A) is the most abundant internal modification in almost all eukaryotic messenger RNAs, and is dynamically regulated. Therefore, identification of m6A readers is especially important in determining the cellular function of m6A. YTHDF2 has recently been characterized as the first m6A reader that regulates the cytoplasmic stability of methylated RNA. Here we show that YTHDC1 is a nuclear m6A reader and report the crystal structure of the YTH domain of YTHDC1 bound to m6A-containing RNA. We further determined the structure of another YTH domain, YTHDF1, and found that the YTH domain utilizes a conserved aromatic cage to specifically recognize the methyl group of m6A. Our structural characterizations of the YTHDC1-m6A RNA complex also shed light on the molecular basis for the preferential binding of the GG(m6A)C sequence by YTHDC1 and confirm the YTH domain as a specific m6A RNA reader. PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) was applied to human YTHDC1 protein to identify its binding sites.
2014-09-18 | E-GEOD-58352 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8681016 | biostudies-literature
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| S-EPMC9310211 | biostudies-literature
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| S-EPMC5416870 | biostudies-literature
Project description:Covalent modifications of RNA and DNA both regulate numerous biological processes, including development and cancer. The most abundant modification of RNA is that of N6-methyladenosine(m6A), while in the case of DNA, the CpG cytosine methylation characterizes cis-regulatory elements for spatial-temporal gene regulation. Recent studies establish a role for RNA m6A in regulating chromatin through histone modifications. However, whether there is also interplay between RNA and DNA methylation remains unknown. We address this question by studying regulation of the primate-specific transposable element (TE), LTR7/HERV-H, that is specifically activated in human embryonic stem cells (hESCs). Exploiting a novel proteomic approach, we find the RNA m6A-reader, YTHDC2, binds to LTR/HERV-H chromatin through interaction with m6A-modified HERV-H transcripts. Significantly, YTHDC2 recruits DNA demethylase, TET1, to activate LTR7/HERV-H via 5-hydroxymethycytosine(5hmC)-mediated DNA methylation. Furthermore, the YTHDC2/LTR7-axis prevents neural conversion of hESCs. Our results establish previously unknown crosstalk between RNA m6A and DNA methylation and new mechanisms controlling TE activity and hESC fate. We focused on the regulation of the primate-specific TE family, LTR7/HERV-H that is specifically active in the pluripotent human embryonic stem cells (hESCs) then silenced in differentiated lineages. We develop CARGO-BioID, a CRISPR-based TE-centric proteomics approach, to identify the proteins associated with thousands of copies of endogenous LTR7/HERV-H loci and potentially regulate their activity in hESCs. We found YTHDC2 and TET1 interact with each other and subsequently regulate m6A level on HERVH transcripts and 5hmC level on HERV-H genomic loci, which is critical for LTR7/HERV-H activities.
2023-05-12 | GSE210859 | GEO
Project description:Covalent modifications of RNA and DNA both regulate numerous biological processes, including development and cancer. The most abundant modification of RNA is that of N6-methyladenosine(m6A), while in the case of DNA, the CpG cytosine methylation characterizes cis-regulatory elements for spatial-temporal gene regulation. Recent studies establish a role for RNA m6A in regulating chromatin through histone modifications. However, whether there is also interplay between RNA and DNA methylation remains unknown. We address this question by studying regulation of the primate-specific transposable element (TE), LTR7/HERV-H, that is specifically activated in human embryonic stem cells (hESCs). Exploiting a novel proteomic approach, we find the RNA m6A-reader, YTHDC2, binds to LTR/HERV-H chromatin through interaction with m6A-modified HERV-H transcripts. Significantly, YTHDC2 recruits DNA demethylase, TET1, to activate LTR7/HERV-H via 5-hydroxymethycytosine(5hmC)-mediated DNA methylation. Furthermore, the YTHDC2/LTR7-axis prevents neural conversion of hESCs. Our results establish previously unknown crosstalk between RNA m6A and DNA methylation and new mechanisms controlling TE activity and hESC fate. We focused on the regulation of the primate-specific TE family, LTR7/HERV-H that is specifically active in the pluripotent human embryonic stem cells (hESCs) then silenced in differentiated lineages. We develop CARGO-BioID, a CRISPR-based TE-centric proteomics approach, to identify the proteins associated with thousands of copies of endogenous LTR7/HERV-H loci and potentially regulate their activity in hESCs. We found YTHDC2 and TET1 interact with each other and subsequently regulate m6A level on HERVH transcripts and 5hmC level on HERV-H genomic loci, which is critical for LTR7/HERV-H activities.
2023-05-12 | GSE224672 | GEO
Project description:Covalent modifications of RNA and DNA both regulate numerous biological processes, including development and cancer. The most abundant modification of RNA is that of N6-methyladenosine(m6A), while in the case of DNA, the CpG cytosine methylation characterizes cis-regulatory elements for spatial-temporal gene regulation. Recent studies establish a role for RNA m6A in regulating chromatin through histone modifications. However, whether there is also interplay between RNA and DNA methylation remains unknown. We address this question by studying regulation of the primate-specific transposable element (TE), LTR7/HERV-H, that is specifically activated in human embryonic stem cells (hESCs). Exploiting a novel proteomic approach, we find the RNA m6A-reader, YTHDC2, binds to LTR/HERV-H chromatin through interaction with m6A-modified HERV-H transcripts. Significantly, YTHDC2 recruits DNA demethylase, TET1, to activate LTR7/HERV-H via 5-hydroxymethycytosine(5hmC)-mediated DNA methylation. Furthermore, the YTHDC2/LTR7-axis prevents neural conversion of hESCs. Our results establish previously unknown crosstalk between RNA m6A and DNA methylation and new mechanisms controlling TE activity and hESC fate. We focused on the regulation of the primate-specific TE family, LTR7/HERV-H that is specifically active in the pluripotent human embryonic stem cells (hESCs) then silenced in differentiated lineages. We develop CARGO-BioID, a CRISPR-based TE-centric proteomics approach, to identify the proteins associated with thousands of copies of endogenous LTR7/HERV-H loci and potentially regulate their activity in hESCs. We found YTHDC2 and TET1 interact with each other and subsequently regulate m6A level on HERVH transcripts and 5hmC level on HERV-H genomic loci, which is critical for LTR7/HERV-H activities.
2023-05-12 | GSE224671 | GEO
Project description:Covalent modifications of RNA and DNA both regulate numerous biological processes, including development and cancer. The most abundant modification of RNA is that of N6-methyladenosine(m6A), while in the case of DNA, the CpG cytosine methylation characterizes cis-regulatory elements for spatial-temporal gene regulation. Recent studies establish a role for RNA m6A in regulating chromatin through histone modifications. However, whether there is also interplay between RNA and DNA methylation remains unknown. We address this question by studying regulation of the primate-specific transposable element (TE), LTR7/HERV-H, that is specifically activated in human embryonic stem cells (hESCs). Exploiting a novel proteomic approach, we find the RNA m6A-reader, YTHDC2, binds to LTR/HERV-H chromatin through interaction with m6A-modified HERV-H transcripts. Significantly, YTHDC2 recruits DNA demethylase, TET1, to activate LTR7/HERV-H via 5-hydroxymethycytosine(5hmC)-mediated DNA methylation. Furthermore, the YTHDC2/LTR7-axis prevents neural conversion of hESCs. Our results establish previously unknown crosstalk between RNA m6A and DNA methylation and new mechanisms controlling TE activity and hESC fate. We focused on the regulation of the primate-specific TE family, LTR7/HERV-H that is specifically active in the pluripotent human embryonic stem cells (hESCs) then silenced in differentiated lineages. We develop CARGO-BioID, a CRISPR-based TE-centric proteomics approach, to identify the proteins associated with thousands of copies of endogenous LTR7/HERV-H loci and potentially regulate their activity in hESCs. We found YTHDC2 and TET1 interact with each other and subsequently regulate m6A level on HERVH transcripts and 5hmC level on HERV-H genomic loci, which is critical for LTR7/HERV-H activities.
2023-05-12 | GSE224670 | GEO
Project description:Covalent modifications of RNA and DNA both regulate numerous biological processes, including development and cancer. The most abundant modification of RNA is that of N6-methyladenosine(m6A), while in the case of DNA, the CpG cytosine methylation characterizes cis-regulatory elements for spatial-temporal gene regulation. Recent studies establish a role for RNA m6A in regulating chromatin through histone modifications. However, whether there is also interplay between RNA and DNA methylation remains unknown. We address this question by studying regulation of the primate-specific transposable element (TE), LTR7/HERV-H, that is specifically activated in human embryonic stem cells (hESCs). Exploiting a novel proteomic approach, we find the RNA m6A-reader, YTHDC2, binds to LTR/HERV-H chromatin through interaction with m6A-modified HERV-H transcripts. Significantly, YTHDC2 recruits DNA demethylase, TET1, to activate LTR7/HERV-H via 5-hydroxymethycytosine(5hmC)-mediated DNA methylation. Furthermore, the YTHDC2/LTR7-axis prevents neural conversion of hESCs. Our results establish previously unknown crosstalk between RNA m6A and DNA methylation and new mechanisms controlling TE activity and hESC fate. We focused on the regulation of the primate-specific TE family, LTR7/HERV-H that is specifically active in the pluripotent human embryonic stem cells (hESCs) then silenced in differentiated lineages. We develop CARGO-BioID, a CRISPR-based TE-centric proteomics approach, to identify the proteins associated with thousands of copies of endogenous LTR7/HERV-H loci and potentially regulate their activity in hESCs. We found YTHDC2 and TET1 interact with each other and subsequently regulate m6A level on HERVH transcripts and 5hmC level on HERV-H genomic loci, which is critical for LTR7/HERV-H activities.
2023-05-12 | GSE224669 | GEO