Cellular and Molecular Life Sciences

, Volume 71, Issue 12, pp 2219-2239

First online:

Synaptic control of local translation: the plot thickens with new characters

  • María Gabriela ThomasAffiliated withInstituto LeloirIIBBA-CONICET
  • , Malena Lucía PascualAffiliated withInstituto LeloirIIBBA-CONICETFacultad de Ciencias Exactas y Naturales, University of Buenos Aires
  • , Darío MaschiAffiliated withInstituto LeloirDepartment of Cell Biology and Physiology, Washington University School of Medicine
  • , Luciana LuchelliAffiliated withInstituto LeloirIIBBA-CONICET
  • , Graciela Lidia BoccaccioAffiliated withInstituto LeloirIIBBA-CONICETFacultad de Ciencias Exactas y Naturales, University of Buenos Aires Email author 

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The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.


mTOR NMDAR ARC/Arg3.1 Abnormal protein aggregation Stress granules EJC