Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification
Activity-regulated cytoskeleton-associated protein (ARC) is activated by the induction of long-term potentiation and plays an important role in the synaptic plasticity of memory consolidation. Previous studies have shown that abnormal expression of ARC in the brains of patients with Alzheimer’s Dise...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.890134/full |
| _version_ | 1817991387760558080 |
|---|---|
| author | Chenhaoyi Xu Huanghuang Huang Min Zhang Pei Zhang Zezhi Li Zezhi Li Xueyuan Liu Min Fang |
| author_facet | Chenhaoyi Xu Huanghuang Huang Min Zhang Pei Zhang Zezhi Li Zezhi Li Xueyuan Liu Min Fang |
| author_sort | Chenhaoyi Xu |
| collection | DOAJ |
| description | Activity-regulated cytoskeleton-associated protein (ARC) is activated by the induction of long-term potentiation and plays an important role in the synaptic plasticity of memory consolidation. Previous studies have shown that abnormal expression of ARC in the brains of patients with Alzheimer’s Disease (AD) leads to the disturbance of synaptic plasticity. ARC expression is mainly regulated by transcriptional and post-translational modification. However, it is unclear whether N6-methyladenosine (m6A) engages in the epigenetic modification of ARC. The AlzData database was used to analyze the brain of AD patients, and Aβ-induced cell models were used. We revealed that ARC expression was reduced in AD patients and Aβ-induced cell models. There were five m6A modification sites of ARC mRNA that were predicted by the SRAMP database, and ARC mRNA was confirmed as the target gene of methyltransferase-like 3 (METTL3) by MeRIP. Amyloid-beta protein (Aβ) repressed the m6A modification. Knockdown of METTL3 decreased ARC mRNA m6A modification and reduced ARC protein expression, while overexpression of METTL3 rescued ARC expression after Aβ treatment. Knockdown of YTH domain family, member 1 (YTHDF1) decreased ARC protein expression, while the overexpression of YTHDF1 could not rescue the loss of ARC protein expression after 3-deazaadenosine treatment or knockdown of METTL3. Our findings identify that METTL3 rescues the Aβ-induced reduction of ARC expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD. |
| first_indexed | 2024-04-14T01:11:38Z |
| format | Article |
| id | doaj.art-eaaf45b6a89f4614954bc8c013a44a50 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-14T01:11:38Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-eaaf45b6a89f4614954bc8c013a44a502022-12-22T02:21:01ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-04-011410.3389/fnagi.2022.890134890134Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine ModificationChenhaoyi Xu0Huanghuang Huang1Min Zhang2Pei Zhang3Zezhi Li4Zezhi Li5Xueyuan Liu6Min Fang7Department of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaThe Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, ChinaDepartment of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaActivity-regulated cytoskeleton-associated protein (ARC) is activated by the induction of long-term potentiation and plays an important role in the synaptic plasticity of memory consolidation. Previous studies have shown that abnormal expression of ARC in the brains of patients with Alzheimer’s Disease (AD) leads to the disturbance of synaptic plasticity. ARC expression is mainly regulated by transcriptional and post-translational modification. However, it is unclear whether N6-methyladenosine (m6A) engages in the epigenetic modification of ARC. The AlzData database was used to analyze the brain of AD patients, and Aβ-induced cell models were used. We revealed that ARC expression was reduced in AD patients and Aβ-induced cell models. There were five m6A modification sites of ARC mRNA that were predicted by the SRAMP database, and ARC mRNA was confirmed as the target gene of methyltransferase-like 3 (METTL3) by MeRIP. Amyloid-beta protein (Aβ) repressed the m6A modification. Knockdown of METTL3 decreased ARC mRNA m6A modification and reduced ARC protein expression, while overexpression of METTL3 rescued ARC expression after Aβ treatment. Knockdown of YTH domain family, member 1 (YTHDF1) decreased ARC protein expression, while the overexpression of YTHDF1 could not rescue the loss of ARC protein expression after 3-deazaadenosine treatment or knockdown of METTL3. Our findings identify that METTL3 rescues the Aβ-induced reduction of ARC expression via YTHDF1-Dependent m6A modification, which suggests an important mechanism of epigenetic alteration in AD.https://www.frontiersin.org/articles/10.3389/fnagi.2022.890134/fullN6-methyladenosine (m6A)methyltransferase-like 3 (METTL3)YTH domain familymember 1 (YTHDF1)activity-regulated cytoskeleton-associated protein (ARC)Alzheimer’s Disease (AD) |
| spellingShingle | Chenhaoyi Xu Huanghuang Huang Min Zhang Pei Zhang Zezhi Li Zezhi Li Xueyuan Liu Min Fang Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification Frontiers in Aging Neuroscience N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) YTH domain family member 1 (YTHDF1) activity-regulated cytoskeleton-associated protein (ARC) Alzheimer’s Disease (AD) |
| title | Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification |
| title_full | Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification |
| title_fullStr | Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification |
| title_full_unstemmed | Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification |
| title_short | Methyltransferase-Like 3 Rescues the Amyloid-beta protein-Induced Reduction of Activity-Regulated Cytoskeleton Associated Protein Expression via YTHDF1-Dependent N6-Methyladenosine Modification |
| title_sort | methyltransferase like 3 rescues the amyloid beta protein induced reduction of activity regulated cytoskeleton associated protein expression via ythdf1 dependent n6 methyladenosine modification |
| topic | N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) YTH domain family member 1 (YTHDF1) activity-regulated cytoskeleton-associated protein (ARC) Alzheimer’s Disease (AD) |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.890134/full |
| work_keys_str_mv | AT chenhaoyixu methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT huanghuanghuang methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT minzhang methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT peizhang methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT zezhili methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT zezhili methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT xueyuanliu methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification AT minfang methyltransferaselike3rescuestheamyloidbetaproteininducedreductionofactivityregulatedcytoskeletonassociatedproteinexpressionviaythdf1dependentn6methyladenosinemodification |