RNA Metabolism in Neurodegenerative Disease

Kathryn      Volkening; Michael      J. Strong

Abstract

RNA metabolism is a vital process through which RNA is produced, transported, regulated, stored, and translated or degraded. Recently, the discoveries of mutations in key RNA binding proteins involved in several human neuronal based diseases have firmly placed the process of RNA metabolism as central to disease etiology. This review first recaps the process of RNA metabolism in the mammalian neuron and describes the roles of RNA granules in this process. Using the recently described alterations in TAR DNA binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) in amyotrophic lateral sclerosis (ALS) and frontal temporal lobar degeneration (FTLD), we discuss how RNA binding protein abnormalities can affect RNA metabolism. We then discuss two additional RNA based mechanisms distinct from alterations in RNA binding protein function that impact RNA metabolism and result in disease. Cumulatively, these observations provide strong support for the hypothesis that alterations in RNA metabolism can lead to neurodegenerative disease, including ALS.

Keywords: ALS, miRNA, FUS/TLS, TDP-43, myotonic dystrophy, spinal muscular atrophy, RNA metabolism, stress granule, transport granule, Neurodegenerative Disease, frontal temporal lobar degeneration, neuronal intermediate filament inclusion diseas, fragile X tremor ataxia syndrome, spinocerebellar ataxia type 8, oculopharyngeal muscular dystrophy