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

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Abstract

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.

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Acknowledgments

We are grateful to MV Baez for kindly providing figure panel 3d and to L Benseñor and LJ Martinez Tosar for their critical reading of the manuscript. This work was supported by the following grants: UBACyT X311 from University of Buenos Aires, Argentina, to GLB; PIP 205-2011-2013 from Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET) to MGT; and PICT 2010-2339, PICT 2010-1850 and PICT 2011-1301 from Agencia Nacional de Promoción Científica y Tecnológica, (ANPCyT), Argentina, to MGT and GLB.

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  1. Darío Maschi

    Present address: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA

Authors and Affiliations

  1. Instituto Leloir, Av. Patricias Argentinas 435, C1405BWE, Buenos Aires, Argentina

    María Gabriela Thomas, Malena Lucía Pascual, Darío Maschi, Luciana Luchelli & Graciela Lidia Boccaccio

  2. IIBBA-CONICET, C1405BWE, Buenos Aires, Argentina

    María Gabriela Thomas, Malena Lucía Pascual, Luciana Luchelli & Graciela Lidia Boccaccio

  3. Facultad de Ciencias Exactas y Naturales, University of Buenos Aires, Buenos Aires, Argentina

    Malena Lucía Pascual & Graciela Lidia Boccaccio

Authors
  1. María Gabriela Thomas
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  2. Malena Lucía Pascual
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  3. Darío Maschi
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  4. Luciana Luchelli
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  5. Graciela Lidia Boccaccio
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Corresponding author

Correspondence to Graciela Lidia Boccaccio.

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M. G. Thomas and M. L. Pascual contributed equally to this work.

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18_2013_1506_MOESM1_ESM.tif

Supplementary material 1 (TIFF 6598 kb) Caption to suggested cover figure. The mRNA repressor Smaug1/Samd4a affects dendritic spines. Dendritic arbors of Smaug1-knockdown hippocampal neurons (yellow) or of untreated cells (white) show the presence of numerous and thin spines provoked by the loss of Smaug1. Deconvoluted confocal Z-stack images of two ECFP-expressing neurons are overlaid

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Thomas, M.G., Pascual, M.L., Maschi, D. et al. Synaptic control of local translation: the plot thickens with new characters. Cell. Mol. Life Sci. 71, 2219–2239 (2014). https://doi.org/10.1007/s00018-013-1506-y

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  • DOI: https://doi.org/10.1007/s00018-013-1506-y

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