Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder
RNA modifications known as epitranscriptomics have emerged as a novel layer of transcriptomic regulation. Like the well-studied epigenetic modifications characterized in DNA and on histone-tails, they have been shown to regulate activity-dependent gene expression and play a vital role in shaping syn...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6220 |
| _version_ | 1797607919412314112 |
|---|---|
| author | Haruka Mitsuhashi Corina Nagy |
| author_facet | Haruka Mitsuhashi Corina Nagy |
| author_sort | Haruka Mitsuhashi |
| collection | DOAJ |
| description | RNA modifications known as epitranscriptomics have emerged as a novel layer of transcriptomic regulation. Like the well-studied epigenetic modifications characterized in DNA and on histone-tails, they have been shown to regulate activity-dependent gene expression and play a vital role in shaping synaptic connections in response to external stimuli. Among the hundreds of known RNA modifications, N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes. Through recognition of its binding proteins, m6A can regulate various aspects of mRNA metabolism and is essential for maintaining higher brain functions. Indeed, m6A is highly enriched in synapses and is involved in neuronal plasticity, learning and memory, and adult neurogenesis. m6A can also respond to environmental stimuli, suggesting an important role in linking molecular and behavioral stress. This review summarizes key findings from fields related to major depressive disorder (MDD) including stress and learning and memory, which suggest that activity-dependent m6A changes may, directly and indirectly, contribute to synaptic connectivity changes underlying MDD. Furthermore, we will highlight the roles of m6A and FTO, a m6A eraser, in the context of depressive-like behaviors. Although we have only begun to explore m6A in the context of MDD and psychiatry, elucidating a link between m6A and MDD presents a novel molecular mechanism underlying MDD pathogenesis. |
| first_indexed | 2024-03-11T05:36:19Z |
| format | Article |
| id | doaj.art-e586ea81d90e4a31930de5273e1cf1b6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:19Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e586ea81d90e4a31930de5273e1cf1b62023-11-17T16:48:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247622010.3390/ijms24076220Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive DisorderHaruka Mitsuhashi0Corina Nagy1McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, CanadaMcGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC H4H 1R3, CanadaRNA modifications known as epitranscriptomics have emerged as a novel layer of transcriptomic regulation. Like the well-studied epigenetic modifications characterized in DNA and on histone-tails, they have been shown to regulate activity-dependent gene expression and play a vital role in shaping synaptic connections in response to external stimuli. Among the hundreds of known RNA modifications, N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes. Through recognition of its binding proteins, m6A can regulate various aspects of mRNA metabolism and is essential for maintaining higher brain functions. Indeed, m6A is highly enriched in synapses and is involved in neuronal plasticity, learning and memory, and adult neurogenesis. m6A can also respond to environmental stimuli, suggesting an important role in linking molecular and behavioral stress. This review summarizes key findings from fields related to major depressive disorder (MDD) including stress and learning and memory, which suggest that activity-dependent m6A changes may, directly and indirectly, contribute to synaptic connectivity changes underlying MDD. Furthermore, we will highlight the roles of m6A and FTO, a m6A eraser, in the context of depressive-like behaviors. Although we have only begun to explore m6A in the context of MDD and psychiatry, elucidating a link between m6A and MDD presents a novel molecular mechanism underlying MDD pathogenesis.https://www.mdpi.com/1422-0067/24/7/6220N6-methyladenosineepitranscriptomicsFTOmajor depressive disorder |
| spellingShingle | Haruka Mitsuhashi Corina Nagy Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder International Journal of Molecular Sciences N6-methyladenosine epitranscriptomics FTO major depressive disorder |
| title | Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder |
| title_full | Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder |
| title_fullStr | Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder |
| title_full_unstemmed | Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder |
| title_short | Potential Roles of m6A and FTO in Synaptic Connectivity and Major Depressive Disorder |
| title_sort | potential roles of m6a and fto in synaptic connectivity and major depressive disorder |
| topic | N6-methyladenosine epitranscriptomics FTO major depressive disorder |
| url | https://www.mdpi.com/1422-0067/24/7/6220 |
| work_keys_str_mv | AT harukamitsuhashi potentialrolesofm6aandftoinsynapticconnectivityandmajordepressivedisorder AT corinanagy potentialrolesofm6aandftoinsynapticconnectivityandmajordepressivedisorder |