The Role of Exon Junction Complexes in Multiple Sclerosis: A Genetic Perspective
Exon junction analysis is an important area of study in understanding complex diseases like Multiple Sclerosis (MS). The exon junction complex (EJC) plays a crucial role in mRNA metabolism by regulating gene expression at various levels, including alternative splicing, translation, mRNA localization, and nonsense-mediated decay. This regulation is critical for proper cell function and can be implicated in disease pathogenesis when dysregulated.
In the context of Multiple Sclerosis, recent studies have explored the relationship between genetic variants and exon splicing. These studies use bioinformatic approaches to identify single-nucleotide polymorphisms (SNPs) that potentially alter splicing patterns in MS. By analyzing gene and exon expression in B cells from MS patients and healthy individuals, researchers can determine how these expressions relate to MS and specific SNPs. This approach provides insights into the molecular mechanisms of MS, revealing how genetic variants associated with the disease might affect pre-mRNA splicing.
One of the key findings in this area is the identification of different classes of splicing events that depend on the EJC and its interaction with other protein complexes. For instance, some splicing events depend solely on the EJC, while others are co-regulated by the EJC and additional complexes like ASAP or PSAP. These interactions suggest that the EJC and its associated proteins can regulate different splicing events, potentially leading to variations in gene expression that might contribute to disease pathology.
Moreover, the EJC is implicated in various physiological roles and diseases, including neurodevelopmental disorders. Its involvement in these processes highlights its significance in the central nervous system and its potential link to neurodegenerative diseases like MS.
Overall, the analysis of exon junctions and their associated complexes offers a promising avenue for understanding the genetic and molecular underpinnings of complex diseases like Multiple Sclerosis. This knowledge can potentially lead to new therapeutic targets and strategies for managing these conditions.
For more detailed information, you can refer to the studies from Nature Reviews Molecular Cell Biology, Scientific Reports, PubMed, MDPI, and Frontiers in Genetics that provide comprehensive insights into the role of exon junction complexes in gene regulation and their implications in diseases like Multiple Sclerosis.
Reference:
Wang, Z., Ballut, L., Barbosa, I., & Le Hir, H. (2018). Exon Junction Complexes can have distinct functional flavours to regulate specific splicing events. Scientific Reports, 8(1), 9509.
Asthana, S., Martin, H., Rupkey, J., Patel, S., Yoon, J., Keegan, A., & Mao, Y. (2022). The physiological roles of the exon junction complex in development and diseases. Cells, 11(7), 1192.
Hir, H. L., Saulière, J., & Wang, Z. (2016). The exon junction complex as a node of post-transcriptional networks. Nature reviews Molecular cell biology, 17(1), 41-54.
Martin, H., Rupkey, J., Asthana, S., Yoon, J., Patel, S., Mott, J., ... & Mao, Y. (2022). Diverse roles of the exon junction complex factors in the cell cycle, cancer, and neurodevelopmental disorders-potential for therapeutic targeting. International journal of molecular sciences, 23(18), 10375.
Putscher, E., Hecker, M., Fitzner, B., Boxberger, N., Schwartz, M., Koczan, D., ... & Zettl, U. K. (2022). Genetic risk variants for multiple sclerosis are linked to differences in alternative pre-mRNA splicing. Frontiers in Immunology, 13, 931831.
Ban, M., Liao, W., Baker, A., Compston, A., Thorpe, J., Molyneux, P., ... & Sawcer, S. (2020). Transcript specific regulation of expression influences susceptibility to multiple sclerosis. European Journal of Human Genetics, 28(6), 826-834.
Jansen, M. I., & Castorina, A. (2023). Identification of Key Genes and Regulatory Pathways in Multiple Sclerosis Brain Samples: A Meta-Analysis of Micro-Array Datasets. International Journal of Molecular Sciences, 24(11), 9361.