Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes
N6-methyladenosine (m6A) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of m6A components appears in a variety of human diseases. RNA m6A modification in Drosophila has proven to b...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/100144 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832589567488688128 |
|---|---|
| author | Shuai Zhang Ruixue Wang Kun Luo Shipeng Gu Xinyu Liu Junhan Wang Ludan Zhang Lin Sun |
| author_facet | Shuai Zhang Ruixue Wang Kun Luo Shipeng Gu Xinyu Liu Junhan Wang Ludan Zhang Lin Sun |
| author_sort | Shuai Zhang |
| collection | DOAJ |
| description | N6-methyladenosine (m6A) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of m6A components appears in a variety of human diseases. RNA m6A modification in Drosophila has proven to be involved in sex determination regulated by Sxl and may affect X chromosome expression through the MSL complex. The dosage-related effects under the condition of genomic imbalance (i.e. aneuploidy) are related to various epigenetic regulatory mechanisms. Here, we investigated the roles of RNA m6A modification in unbalanced genomes using aneuploid Drosophila. The results showed that the expression of m6A components changed significantly under genomic imbalance, and affected the abundance and genome-wide distribution of m6A, which may be related to the developmental abnormalities of aneuploids. The relationships between methylation status and classical dosage effect, dosage compensation, and inverse dosage effect were also studied. In addition, we demonstrated that RNA m6A methylation may affect dosage-dependent gene regulation through dosage-sensitive modifiers, alternative splicing, the MSL complex, and other processes. More interestingly, there seems to be a close relationship between MSL complex and RNA m6A modification. It is found that ectopically overexpressed MSL complex, especially the levels of H4K16Ac through MOF, could influence the expression levels of m6A modification and genomic imbalance may be involved in this interaction. We found that m6A could affect the levels of H4K16Ac through MOF, a component of the MSL complex, and that genomic imbalance may be involved in this interaction. Altogether, our work reveals the dynamic and regulatory role of RNA m6A modification in unbalanced genomes, and may shed new light on the mechanisms of aneuploidy-related developmental abnormalities and diseases. |
| format | Article |
| id | doaj-art-be17f5ce407a4619a0107906c2ef25ab |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-be17f5ce407a4619a0107906c2ef25ab2025-01-24T13:07:10ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.100144Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomesShuai Zhang0Ruixue Wang1https://orcid.org/0000-0001-5046-5023Kun Luo2Shipeng Gu3Xinyu Liu4Junhan Wang5Ludan Zhang6Lin Sun7https://orcid.org/0000-0002-8827-8319Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaKey Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing, China; Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing, ChinaN6-methyladenosine (m6A) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of m6A components appears in a variety of human diseases. RNA m6A modification in Drosophila has proven to be involved in sex determination regulated by Sxl and may affect X chromosome expression through the MSL complex. The dosage-related effects under the condition of genomic imbalance (i.e. aneuploidy) are related to various epigenetic regulatory mechanisms. Here, we investigated the roles of RNA m6A modification in unbalanced genomes using aneuploid Drosophila. The results showed that the expression of m6A components changed significantly under genomic imbalance, and affected the abundance and genome-wide distribution of m6A, which may be related to the developmental abnormalities of aneuploids. The relationships between methylation status and classical dosage effect, dosage compensation, and inverse dosage effect were also studied. In addition, we demonstrated that RNA m6A methylation may affect dosage-dependent gene regulation through dosage-sensitive modifiers, alternative splicing, the MSL complex, and other processes. More interestingly, there seems to be a close relationship between MSL complex and RNA m6A modification. It is found that ectopically overexpressed MSL complex, especially the levels of H4K16Ac through MOF, could influence the expression levels of m6A modification and genomic imbalance may be involved in this interaction. We found that m6A could affect the levels of H4K16Ac through MOF, a component of the MSL complex, and that genomic imbalance may be involved in this interaction. Altogether, our work reveals the dynamic and regulatory role of RNA m6A modification in unbalanced genomes, and may shed new light on the mechanisms of aneuploidy-related developmental abnormalities and diseases.https://elifesciences.org/articles/100144aneuploidym6Aunbalanced genomesepigenetics |
| spellingShingle | Shuai Zhang Ruixue Wang Kun Luo Shipeng Gu Xinyu Liu Junhan Wang Ludan Zhang Lin Sun Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes eLife aneuploidy m6A unbalanced genomes epigenetics |
| title | Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes |
| title_full | Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes |
| title_fullStr | Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes |
| title_full_unstemmed | Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes |
| title_short | Dynamics and regulatory roles of RNA m6A methylation in unbalanced genomes |
| title_sort | dynamics and regulatory roles of rna m6a methylation in unbalanced genomes |
| topic | aneuploidy m6A unbalanced genomes epigenetics |
| url | https://elifesciences.org/articles/100144 |
| work_keys_str_mv | AT shuaizhang dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT ruixuewang dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT kunluo dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT shipenggu dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT xinyuliu dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT junhanwang dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT ludanzhang dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes AT linsun dynamicsandregulatoryrolesofrnam6amethylationinunbalancedgenomes |