title: Local RNA translation at the synapse and in disease.
abstract: Local regulation of protein synthesis in neurons has emerged as a leading research focus because of its importance in synaptic plasticity and neurological diseases. The complexity of neuronal subcellular domains and their distance from the soma demand local spatial and temporal control of protein synthesis. Synthesis of many synaptic proteins, such as GluR and PSD-95, is under local control. mRNA binding proteins (RBPs), such as FMRP, function as key regulators of local RNA translation, and the mTORC1 pathway acts as a primary signaling cascade for regulation of these proteins. Much of the regulation occurs through structures termed RNA granules, which are based on reversible aggregation of the RBPs, some of which have aggregation prone domains with sequence features similar to yeast prion proteins. Mutations in many of these RBPs are associated with neurological diseases, including FMRP in fragile X syndrome; TDP-43, FUS (fused in sarcoma), angiogenin, and ataxin-2 in amyotrophic lateral sclerosis; ataxin-2 in spinocerebellar ataxia; and SMN (survival of motor neuron protein) in spinal muscular atrophy.
authors.affiliation: Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Liu-Yesucevitz
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Gitler
authors.forename: Anne C
authors.initials: AC
authors.lastname: Hart
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
authors.forename: Joel D
authors.initials: JD
authors.lastname: Richter
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Warren
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wolozin
mesh_terms: D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012313:RNA
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