The EJC factor eIF4AIII modulates synaptic strength and neuronal protein expression.
Proper neuronal function and several forms of synaptic plasticity are highly dependent on precise control of mRNA translation, particularly in dendrites. We find that eIF4AIII, a core exon junction complex (EJC) component loaded onto mRNAs by pre-mRNA splicing, is associated with neuronal mRNA granules and dendritic mRNAs. eIF4AIII knockdown markedly increases both synaptic strength and GLUR1 AMPA receptor abundance at synapses. eIF4AIII depletion also increases ARC, a protein required for maintenance of long-term potentiation; arc mRNA, one of the most abundant in dendrites, is a natural target for nonsense-mediated decay (NMD). Numerous new NMD candidates, some with potential to affect synaptic activity, were also identified computationally. Two models are presented for how translation-dependent decay pathways such as NMD might advantageously function as critical brakes for protein synthesis in cells such as neurons that are highly dependent on spatially and temporally restricted protein expression.
Giorgi
Corinna
C
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, MA 02454, USA.
Yeo
Gene W
GW
Stone
Martha E
ME
Katz
Donald B
DB
Burge
Christopher
C
Turrigiano
Gina
G
Moore
Melissa J
MJ
D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007438:Introns; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012322:RNA Precursors / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D020413:3' Untranslated Regions; D003598:Cytoskeletal Proteins; D039601:Eukaryotic Initiation Factor-4A; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; D011993:Recombinant Fusion Proteins; C492186:Stau1 protein, rat; C092069:activity regulated cytoskeletal-associated protein