Translation regulation at the synapse: the plot thickens with multiple characters (COVER ARTICLE)

THOMAS, M.GABRIELA; PASCUAL, MALENA; MASCHI, D; LUCHELLI, LUCIANA; BOCCACCIO, GRACIELA L

CELLULAR AND MOLECULAR LIFE SCIENCES

BIRKHAUSER VERLAG AG

Lugar: BASEL; Año: 2014 p. 1 - 21

1420-682X

The local production of proteins that ultimately control the strength of the synaptic transmission contributes to memory formation, and regulated transcription, transport and mRNA processing provide dynamic control of the dendritic transcriptome. Local translation is modulated by synaptic activity and by a complex network of RNA-binding proteins (RBPs) and various kinds of non-coding RNAs -including BC-RNAs, miRNAs, piRNAs, siRNAs and 5´tRNAs- thereby affecting behavior and cognitive functions. The RBPs FMRP and CPEB play a well-established role in synaptic translation and additional RNA regulatory factors are emerging. The mRNA repressors Smaug, Nanos and Pumilio define a novel pathway for local translational control that affects dendritic spines and branching in mammals and flies. The dynamic aggregation of mRNA regulators into Processing Bodies (PBs) and related neuronal mRNA-silencing foci containing repressed mRNAs is a common theme. Synaptic mRNA-silencing foci (SyAS foci) differentially respond to specific stimuli with changes in their integrity, thus allowing regulated mRNA release followed by translation. Compelling evidence has been presented that the self-aggregation of mRNA repressors directed by specific protein regions has important consequences in synapse function. Multimerization by polyQ expansions and additional low-complexity regions present in CPEB, Pumilio, TDP43, FUS/TLS and other relevant RBPs are related to neurodegeneration, thus linking mRNA-silencing foci dynamics with pathogenic processes. Here we summarize the current knowledge on translation regulation at the synapse with focus on specific RBPs and mRNA-silencing foci dynamics.