| MEX3B | |
|---|---|
| Gene Symbol | MEX3B |
| Full Name | MEX3 RNA Binding Family Member B |
| Chromosomal Location | 11q22.2 |
| NCBI Gene ID | [55607](https://www.ncbi.nlm.nih.gov/gene/55607) |
| Ensembl ID | ENSG00000178297 |
| UniProt | [Q8IZL8](https://www.uniprot.org/uniprot/Q8IZL8) |
| OMIM | [611949](https://www.omim.org/entry/611949) |
| Protein Class | RNA-binding protein |
MEX3B (MEX3 RNA Binding Family Member B) is an RNA-binding protein that plays critical roles in post-transcriptional gene regulation, innate immune signaling, and RNA metabolism[1]. Like other MEX3 family members, MEX3B contains KH domains that enable sequence-specific binding to RNA and regulate mRNA translation, stability, and subcellular localization[2].
In the context of neurodegenerative diseases, MEX3B is of particular interest due to its involvement in RNA metabolism pathways disrupted in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)[3]. These disorders share common pathological features including TDP-43 proteinopathy, providing a mechanistic link between MEX3B dysfunction and disease pathogenesis.
MEX3B encodes an RNA-binding protein with multiple cellular functions[2:1]:
MEX3B functions in innate immune pathways[4][5]:
Under cellular stress conditions, MEX3B regulates the stress response[6]:
MEX3B is genetically and functionally associated with ALS and FTD[7][3:1]:
The connection to TDP-43 pathology is particularly significant since TDP-43 inclusions are found in 95% of ALS cases and ~50% of FTD cases[10][11].
MEX3B modulates neuroinflammatory responses in the central nervous system[12][13]:
RNA-binding proteins like MEX3B represent attractive therapeutic targets[14][15]:
MEX3B is expressed throughout the nervous system[16]:
| Disease | Role | Evidence |
|---|---|---|
| ALS | Genetic modifier | GWAS[7:1] |
| FTD | Genetic modifier | GWAS |
| ALS/FTD spectrum | Shared pathways | Functional studies |
| Neuroinflammation | Modulator | Expression studies |
Buchet-Poyau K, et al. Identification and characterization of human MEX3 proteins, a novel family of RNA-binding proteins. Journal of Molecular Biology. 2002. ↩︎
D'Agostino VG, et al. The RNA-binding protein MEX3B: A key regulator of translation and tumor progression. Cellular and Molecular Life Sciences. 2021. ↩︎ ↩︎
Liu-Yesucevitz L, et al. RNA binding proteins and the pathology of ALS. Brain Research. 2020. ↩︎ ↩︎
Liu Z, et al. MEX3B mediates RNA virus-triggered autophagy. Cell Death & Disease. 2022. ↩︎
Hiscott J, et al. Convergence of the NF-kappaB and interferon signaling pathways. Cellular and Molecular Biology. 2005. ↩︎ ↩︎
Cruz T, et al. Cellular stress response and MEX3B expression. Free Radical Biology & Medicine. 2020. ↩︎
Benatar M, et al. ALS genetic modifiers: A genome-wide association study. Neurology. 2023. ↩︎ ↩︎
Dormann D, et al. TDP-43: a novel target for therapeutic development in ALS and FTD. EMBO Molecular Medicine. 2010. ↩︎
Kabashi E, et al. TARDBP mutations in amyotrophic lateral sclerosis. Nature Genetics. 2010. ↩︎
Ratti A, et al. TDP-43 pathology in ALS and FTD. Acta Neuropathologica. 2015. ↩︎
Highley JR, et al. Loss of TDP-43 function in neurodegeneration. Nature Reviews Neurology. 2021. ↩︎
Heneka MT, et al. Neuroinflammation in neurodegenerative disease. Nature Reviews Neurology. 2019. ↩︎
Amoroso MW, et al. Neuroinflammation and RNA-binding proteins in ALS. Journal of Neuroinflammation. 2022. ↩︎
Sivakumar K, et al. RNA-targeted therapies for ALS. Neurotherapeutics. 2023. ↩︎
Latour-Mioc A, et al. Immunomodulation in neurodegeneration. Brain. 2021. ↩︎
Ziats MN, et al. Comprehensive analysis of gene expression in the human brain. Brain Research. 2016. ↩︎