The role of ZC3H14 (MSUT2) in neurodevelopment and tauopathies

Abstract The process of neurodevelopment and neuropathology can be influenced by RNA binding proteins. The RNA binding protein ZC3H14 (also referred to as MSUT2) is of particular interest for two reasons. First, homozygous loss-of function alleles in ZC3H14 are associated with an inherited form of intellectual disability. Second, in model systems, loss of ZC3H14 can suppress the toxicity of tau aggregates, which are hallmark diagnostic features of Alzheimer’s disease and other neurodegenerative diseases referred to as “tauopathies”. In this review, we discuss both the normal functions of ZC3H14 and how alterations in these functions may affect cognitive function or tau pathology. Although not fully understood, an emerging theme is that alterations in RNA regulation due to ZC3H14 loss can affect neuronal function.