EEF1A2 is a gene that provides instructions for making a protein known as eukaryotic elongation factor 1 alpha 2 (eEF1A2). This protein is a component of the elongation factor-1 complex, which plays a role in cellular machinery. While eEF1A2 is present throughout the body, its expression is particularly notable in certain tissues. This protein is found in high amounts within the brain, heart, and skeletal muscle tissues, highlighting its importance for bodily function.
How EEF1A2 Works
The function of eEF1A2 centers around protein synthesis, a biological process where cells build new proteins. This process, known as translation elongation, involves the ribosome, the cellular machinery responsible for reading genetic instructions and assembling amino acids into protein chains. eEF1A2 acts as a delivery system, ensuring that the correct amino acids arrive at the ribosome at the right time.
Imagine protein synthesis as an assembly line where amino acids are the building blocks and the ribosome is the factory. eEF1A2, a GTP-binding protein, acts like a forklift, picking up individual amino acids attached to transfer RNA (tRNA) molecules. It then guides this aminoacyl-tRNA complex to the ribosome’s A-site, where the amino acid is added to the growing protein chain. This process relies on the hydrolysis of guanosine triphosphate (GTP) for energy, which eEF1A2 facilitates, ensuring the efficient and accurate addition of each new amino acid. The action of eEF1A2 is therefore important for cellular functions that depend on newly made proteins.
The eEF1A protein family includes two isoforms in mammals: eEF1A1 and eEF1A2. While eEF1A1 is widely expressed across most tissues, eEF1A2 exhibits a more restricted expression pattern, primarily found in neurons and muscle cells. This tissue-specific expression suggests that eEF1A2 may have specialized roles beyond its general function in protein synthesis, particularly in these active cell types. The two isoforms are similar, sharing over 90% DNA sequence and amino acid identity, but their distinct expression patterns imply contributions to cellular processes.
EEF1A2 and Brain Health
The presence of eEF1A2 in the brain underscores its role in neurological function. It is important for the development and proper functioning of neurons, the cells that transmit information throughout the nervous system. This protein contributes to synaptic plasticity, the ability of synapses—the connections between neurons—to strengthen or weaken over time, underlying learning and memory.
Dysregulation or mutations in the EEF1A2 gene are linked to several neurological conditions. Harmful variants in EEF1A2 are associated with early infantile epileptic encephalopathy 33 (EIEE33), also known as developmental and epileptic encephalopathy 33 (DEE33). This condition often presents with severe developmental delay, epilepsy, and intellectual disability, with seizures typically beginning within the first four months of life. The location and nature of these mutations can influence the severity of the clinical presentation; missense mutations affecting key protein domains often lead to earlier onset and more severe epilepsy.
Further neurological impacts of EEF1A2 mutations can include movement disorders, such as dystonia, and a degenerative course. The consequences of impaired eEF1A2 function in the nervous system are significant, affecting not only protein synthesis but also other cellular processes like actin remodeling, important for structural modifications in dendritic spines during synaptic plasticity. The loss of eEF1A2 function in mice has been observed to lead to neurodegeneration and neuromuscular abnormalities, highlighting its importance for nervous system health.
EEF1A2 Beyond the Brain
Beyond its roles in the brain, eEF1A2 is recognized for its involvement in other bodily systems and various diseases. While its role in protein synthesis is universal, its dysregulation can have tissue-specific consequences. eEF1A2 is also studied in certain types of cancer.
Overexpression of eEF1A2 has been observed in various tumors, including breast, ovarian, and lung tumors. For instance, it is overexpressed in approximately 60% of breast tumors, suggesting a potential role in cancer development. This overexpression may activate pathways that promote tumorigenesis and inhibit apoptosis, programmed cell death.
The oncogenic potential of eEF1A2 might stem from its involvement in protein synthesis, which supports the growth of cancer cells, or from its non-canonical functions. These non-canonical functions include interactions with the cytoskeleton, affecting cell invasion, migration, and its ability to activate signaling pathways like Akt, which influences cell proliferation and survival. Studies have shown that forcing eEF1A2 expression can lead to tumorigenic properties, supporting its role in cancer progression.
Advancing Our Knowledge of EEF1A2
Research focuses on understanding EEF1A2 mechanisms in healthy function and disease. Scientists are exploring how different harmful variants in the EEF1A2 gene lead to neurological conditions like epilepsy and intellectual disability. This research aims to clarify whether mutations reduce protein function or produce a toxic product, a distinction important for targeted treatments.
Diagnostic approaches are being refined, with genetic testing, such as whole exome sequencing, playing a role in identifying EEF1A2 mutations in individuals with unexplained developmental delays and epilepsy. Researchers are investigating therapeutic strategies to modulate eEF1A2 activity. One area involves antisense oligonucleotide (ASO) therapy, which aims to reduce faulty eEF1A2 protein levels in affected nerve and muscle cells. These studies, including preclinical investigations of drug and genetic therapies, are laying the groundwork for future interventions that could improve outcomes for individuals affected by EEF1A2-related disorders.