- MEX3C is a protein-coding gene that belongs to the MEX-3 family of RNA-binding proteins, originally identified in Caenorhabditis elegans as key regulators of embryonic cell fate.
- In humans, MEX3C is located on chromosome 18q21.2 and encodes a protein with dual functional domains: two K-homology (KH) RNA-binding domains, which allow interaction with specific mRNA targets, and a C-terminal RING finger domain, which confers E3 ubiquitin ligase activity. This structural combination enables MEX3C to regulate gene expression at both the post-transcriptional (mRNA stability, localization, and translation) and post-translational (protein ubiquitination and degradation) levels, making it a multifunctional regulator in cellular processes.
- Functionally, MEX3C has been implicated in diverse biological pathways. As an RNA-binding protein, it regulates the stability and translation of target transcripts involved in cell growth, differentiation, and metabolism. Its ubiquitin ligase activity further contributes to protein turnover, impacting signaling pathways that control immune responses, development, and tumorigenesis. Recent research has highlighted a role for MEX3C in innate immunity, particularly in the regulation of antiviral responses, where it modulates the activity of RIG-I-like receptors and interferon signaling. It has also been linked to metabolic regulation, influencing pathways associated with adipogenesis and energy balance, and has been studied as a candidate gene associated with obesity and metabolic syndrome.
- In the context of disease, dysregulation of MEX3C expression or function has been associated with several pathological conditions. In oncology, MEX3C is thought to contribute to cancer progression through its influence on RNA and protein networks that regulate proliferation, apoptosis, and metastasis. For example, altered MEX3C expression has been observed in gastric cancer, colorectal cancer, and glioblastoma, where it may act as an oncogenic factor by destabilizing tumor suppressor mRNAs or promoting oncogenic signaling. Additionally, genome-wide association studies (GWAS) have implicated MEX3C variants in susceptibility to obesity, insulin resistance, and type 2 diabetes, reflecting its role in metabolic homeostasis.
- MEX3C also has emerging roles in neurodevelopment and neuronal plasticity, as RNA-binding proteins are key regulators of localized translation in neurons. While research is still in its early stages, evidence suggests that MEX3C, along with other MEX-3 family members, may participate in the fine-tuning of synaptic function and brain development, although the specific mechanisms remain to be fully elucidated.
- Given its dual RNA-binding and ubiquitin ligase activities, MEX3C represents an important regulatory hub at the intersection of RNA biology and protein homeostasis. Ongoing research aims to clarify its physiological targets, its role in signaling pathways, and its potential as a therapeutic target in metabolic disorders, immune dysregulation, and cancer.
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