N-6 Methyladenosine in Oligodendrocytes

 

Oligodendrocytes are essential for myelination of axons in the CNS and allow for rapid saltatory conduction. They develop from oligodendrocyte precursor cells (OPCs) in areas of the embryonic neural tube and will proliferate and differentiate into pre-myelinating oligodendrocytes. After a series of morphological changes, pre-myelinating oligodendrocytes will express major myelinating proteins that allow for several processes during myelination. For any of these processes to occur, the RNA modifier N⁶-methyladenosine (m⁶A) and its components must make modifications. Disruption of the modification process by removing readers, writers, or other components can cause disruption of oligodendrocytes. The reader, Prrc2a, along with the coder, Mettl14, have both been identified as critical components to N⁶-methyladenosine’s role in oligodendrocyte production.

The article “A Novel m⁶A reader Prrc2a Controls Oligodendroglial Specification and Myelination” by Rong Wu and others touches on the m⁶A reader, Prrc2A, and its effects on oligodendrocytes. Proline rich coiled-coil 2 A (Prrc2A) is an N⁶-methyladenosine reader that controls specification, myelination, proliferation, and fate determination of oligodendrocytes. The study found that the removal of Prrc2a caused development delays, increased brain mass, lower body mass, abnormal brain structures, and enlarged lateral ventricles. Further, It was discovered that Prrc2a is highly expressed in oligodendrocyte precursor cells. Interestingly, Prrc2a knockout mice did not exhibit major changes in the number of neurons they had. It was also found that deficiency of Prrc2a had effects on the gene expression and that thousands of differentially expressed genes (DEG’s) were detected. Similarly, the article “m⁶A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination”  by Huan Xu and others discusses another m⁶A component, Mettl14, and its effect on oligodendrocytes. Mettl14 is a coder for essential writer components of N⁶-methyladenosine and is critical for regulation of oligodendrocyte development and myelination in the CNS. The study determined that deletion of Mettl14 was found to cause myelin abnormalities and lower amounts of oligodendrocytes in mice. Further, though mature oligodendrocyte levels in the Mettl14 knockout mice were low, they did not find a reduction in OPC’s. Additionally, the corpus callosum in the Mettl14 deficient mice exhibited patchy myelin and a visible reduction in oligodendrocytes

Both the articles suggest that disruption of readers, writers, coders, or other components of N⁶-methyladenosine has profound effects on the central nervous system. Studies like these are crucial for finding how N⁶-methyladenosine affects the nervous system. More information about m⁶A may aid in the research of myelin-related or congenital disorders affecting oligodendrocytes and could potentially progress treatment options or preventative measures. N⁶-methyladenosine related studies can also uncover its contributions to other areas of the nervous system and body, aiding in the comprehension of disorders that result as a consequence of N⁶-methyladenosine mutation. Overall, it is clear that N⁶-methyladenosine is critical for normal development of oligodendrocytes and can have extreme effects on the body when one of its components mutates.

 

 

 

 

1.          Xu H, Dzhashiashvili Y, Shah A, et al. m6A mRNA Methylation Is Essential for Oligodendrocyte Maturation and CNS Myelination. Neuron. 2020;105(2):293-309.e5. doi: https://doi.org/10.1016/j.neuron.2019.12.013

2.          Wu R, Li A, Sun B, et al. A novel m6A reader Prrc2a controls oligodendroglial specification and myelination. Cell Research. 2019;29(1):23-41. doi: https://doi.org/10.1038/s41422-018-0113-8