Tubulin beta-4A chain mRNA (TUBB4A mRNA) (TUBB4A mRNA)

TUBB4A mRNA is the transcript of the TUBB4A gene, which encodes the beta-4A tubulin subunit, a primary component of microtubules highly expressed in the central nervous system, particularly within oligodendrocytes (UniProt P04350). These microtubules are vital for maintaining cellular architecture, facilitating intracellular transport, and supporting the myelination process (PubMed: 23911918). Mutations in the TUBB4A gene, such as the common p.Asp249Asn variant, cause a spectrum of neurodegenerative leukodystrophies, most notably Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), characterized by a toxic gain-of-function that disrupts microtubule dynamics (PubMed: 32037394). Because the disease is often driven by the presence of the mutant protein, the mRNA transcript has become a therapeutic target for antisense oligonucleotides (ASOs) like ION464 (also known as BIIB129). These ASOs are designed to bind to the TUBB4A mRNA and trigger its degradation via RNase H, thereby reducing the production of the toxic tubulin protein and potentially halting disease progression (Ionis Pharmaceuticals, 2023). By lowering the levels of the aberrant protein, the therapy aims to restore normal cellular function and halt the progression of neurodegeneration.

Other names

TUBB4 mRNATubulin beta-4 chain mRNATbeta4 mRNABeta-4 tubulin mRNATUBB4A transcript

Antisense oligonucleotide-mediated degradation of mRNA via RNase H1 recruitment to reduce toxic protein expression.