Selective neuronal vulnerability to deficits in RNA processing

Emerging evidence indicates that errors in RNA processing can causally drive neurodegeneration. Given that RNA produced from expressed genes of all cell types undergoes processing (splicing, polyadenylation, 5′ capping, etc.), the particular vulnerability of neurons to deficits in RNA processing calls for careful consideration. The activity-dependent transcriptome remodeling associated with synaptic plasticity in neurons requires rapid, multilevel post-transcriptional RNA processing events that provide additional opportunities for dysregulation and consequent introduction or persistence of errors in RNA transcripts. Here we review the accumulating evidence that neurons have an enhanced propensity for errors in RNA processing alongside grossly insufficient defenses to clear misprocessed RNA compared to other cell types. Additionally, we explore how tau, a microtubule-associated protein implicated in Alzheimer's disease and related tauopathies, contributes to deficits in RNA processing and clearance.