Mammalian suppressor of tauopathy 2 (MSUT2) messenger RNA (MSUT2 mRNA)

Mammalian suppressor of tauopathy 2 (MSUT2) messenger RNA is an emerging therapeutic target for neurodegenerative diseases characterized by tau protein aggregation, such as Alzheimer's disease and frontotemporal dementia (Wheeler et al., 2019). MSUT2 is the mammalian ortholog of the C. elegans gene sut-2 and encodes a zinc finger CCCH-type protein, also known as ZC3H14, which functions as a poly(A) RNA-binding protein involved in RNA processing and polyadenylation (Guthrie et al., 2011; UniProt Q6PJT7). Research has demonstrated that MSUT2 levels are significantly upregulated in the brains of Alzheimer's patients, particularly in areas affected by tau pathology, and its expression correlates with the progression of the disease. Experimental knockdown of MSUT2 mRNA using antisense oligonucleotides (ASOs) or RNA interference has been shown to reduce tau aggregation and protect against neurodegeneration in animal models, suggesting that MSUT2 acts as a co-factor that promotes tau toxicity. Consequently, targeting the MSUT2 mRNA to lower protein levels represents a viable strategy for gene-silencing therapies in tauopathies. However, therapeutic development must account for the fact that loss-of-function mutations in the human ZC3H14 gene are linked to non-syndromic autosomal recessive intellectual disability, indicating a critical role for the protein in normal brain development and function (Pak et al., 2011). Therefore, any therapeutic intervention must carefully balance the reduction of pathological tau toxicity with the preservation of essential MSUT2-mediated RNA processing functions.

Other names

Zinc finger CCCH domain-containing protein 14 mRNAZC3H14 mRNASuppressor of tauopathy 2 mRNASUT2 mRNA

RNase H-mediated degradation of target mRNA or RNA interference-mediated silencing