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      Influence of N6-Methyladenosine Modification Gene HNRNPC on Cell Phenotype in Parkinson's Disease

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      Parkinson's Disease
      Hindawi

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          Abstract

          This study aimed to explore the N6-methyladenosine (m6A) modification genes involved in the pathogenesis of Parkinson's disease (PD) through data analysis of the two data sets GSE120306 and GSE22491 in the GEO database and further explore its influence on cell phenotype in PD. We analyzed the differentially expressed genes and function enrichment analysis of the two sets of data and found that the expression of the m6A-modification gene HNRNPC was significantly downregulated in the PD group, and it played an important role in DNA metabolism, RNA metabolism, and RNA processing and may be involved in PD. Then, we constructed the HNRNPC differential expression cell line to study the role of this gene in the pathogenesis of PD. The results showed that overexpression of HNRNPC can promote the proliferation of PC12 cells, inhibit their apoptosis, and inhibit the expression of inflammatory factors IFN- β, IL-6, and TNF- α, suggesting that HNRNPC may cause PD by inhibiting the proliferation of dopaminergic nerve cells, promoting their apoptosis, and causing immune inflammation. Our study also has certain limitations. For example, the data of the experimental group and the validation group come from different cell types, and the data of the experimental group involve individuals with G2019S LRRK2 mutations. In addition, due to the low expression of HNRNPC in PC12 cells, we used the method of overexpressing this gene to study its function. All these factors may cause our conclusions to be biased. Therefore, more research is still needed to corroborate it in the future.

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          Most cited references53

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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            m6A-dependent regulation of messenger RNA stability

            N6 -methyladenosine (m6A) is the most prevalent internal (non-cap) modification present in the messenger RNA (mRNA) of all higher eukaryotes 1,2 . Although essential to cell viability and development 3–5 , the exact role of m6A modification remains to be determined. The recent discovery of two m6A demethylases in mammalian cells highlighted the importance of m6A in basic biological functions and disease 6–8 . Here we show that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m6A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies 9 . The C-terminal domain of YTHDF2 selectively binds to m6A-containing mRNA whereas the N-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m6A modification is recognized by selective-binding proteins to affect the translation status and lifetime of mRNA.
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              N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

              We report here that FTO (fat mass and obesity-associated protein) exhibits efficient oxidative demethylation activity of abundant N 6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to an increased level of m6A in mRNA, whereas overexpression of FTO resulted in a decreased level of m6A in human cells. We further show that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
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                Author and article information

                Contributors
                Journal
                Parkinsons Dis
                Parkinsons Dis
                pd
                Parkinson's Disease
                Hindawi
                2090-8083
                2042-0080
                2021
                20 December 2021
                : 2021
                : 9919129
                Affiliations
                Department of Neurology, China–Japan Union Hospital of Jilin University, No. 126, Xian Tai Road, Changchun, Jilin 130000, China
                Author notes

                Academic Editor: Cristine Alves da Costa

                Author information
                https://orcid.org/0000-0002-0863-7060
                https://orcid.org/0000-0002-3422-2125
                https://orcid.org/0000-0002-0303-3241
                https://orcid.org/0000-0003-4861-7619
                https://orcid.org/0000-0002-2576-1485
                https://orcid.org/0000-0001-6241-0804
                https://orcid.org/0000-0003-1065-9952
                Article
                10.1155/2021/9919129
                8712163
                e4161f05-5bda-44ba-b59f-495bfa5ff493
                Copyright © 2021 Wei Quan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 September 2021
                : 3 December 2021
                : 7 December 2021
                Funding
                Funded by: Department of Finance of Jilin Province
                Award ID: 20190201213JC
                Funded by: Department of Science and Technology of Jilin Province
                Award ID: 20200201451JC
                Categories
                Research Article

                Neurology
                Neurology

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