Local RNA translation at the synapse and in disease

Liqun Liu-Yesucevitz, Gary J. Bassell, Aaron D. Gitler, Anne C. Hart, Eric Klann, Joel D. Richter, Stephen T. Warren, Benjamin Wolozin

Research output: Contribution to journalArticlepeer-review

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 inmanyof these RBPs are associated with neurological diseases, includingFMRPin fragileXsyndrome; 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.

Original languageEnglish (US)
Pages (from-to)16086-16093
Number of pages8
JournalJournal of Neuroscience
Volume31
Issue number45
DOIs
StatePublished - Nov 9 2011

ASJC Scopus subject areas

  • General Neuroscience

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