Translation Efficiency of Synaptic Proteins and Its Coding Sequence Determinants

Shelly Mahlab, Itai Linial, Michal Linial

Abstract

The synapse is an organized structure that contains synaptic vesicles, mitochondria, receptors, transporters and stored proteins. About 10% of the mRNAs that are express in mammalian neurons are delivered to synaptic sites, where they are subjected to local translation. While neuronal plasticity, learning and memory occur at the synapse, the mechanisms that regulate post-transcriptional events and local translation are mostly unknown. We hypothesized that evolutional signals that govern translational efficiency are encoded in the mRNA of synaptic proteins. Specifically, we applied a measure of tRNA adaptation index (tAI) as an indirect proxy for translation rate and showed that ionic channels and ligand-binding receptors are specified by a global low tAI values. In contrast, the genuine proteins of the synaptic vesicles exhibit significantly higher tAI values. The expression of many of these proteins actually accompanied synaptic plasticity. Furthermore, in human, the local tAI values for the initial segment of mRNA coding differs for synaptic proteins in view of the rest of the human proteome. We propose that the translation of synaptic proteins is a robust solution for compiling with the high metabolic demands of the synapse.

References

  1. Ames, A., 3rd (1992) Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies on retina, Can J Physiol Pharmacol, 70 Suppl, S158-164.
  2. Arava, Y., et al. (2003) Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae, Proc Natl Acad Sci U S A, 100, 3889-3894.
  3. Barrell, D., et al. (2009) The GOA database in 2009-an integrated Gene Ontology Annotation resource, Nucleic Acids Res, 37, D396-403.
  4. Brachya, G., et al. (2006) Synaptic proteins as multisensor devices of neurotransmission, BMC Neurosci, 7 Suppl 1, S4.
  5. Broadie, K.S. and Richmond, J.E. (2002) Establishing and sculpting the synapse in Drosophila and C. elegans, Curr Opin Neurobiol, 12, 491-498.
  6. Cajigas, I.J., et al. (2012) The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging, Neuron, 74, 453-466.
  7. Chiti, F. and Dobson, C.M. (2006) Protein misfolding, functional amyloid, and human disease, Annu Rev Biochem, 75, 333-366.
  8. dos Reis, M., et al. (2004) Solving the riddle of codon usage preferences: a test for translational selection, Nucleic Acids Res, 32, 5036-5044.
  9. Ferro-Novick, S. and Jahn, R. (1994) Vesicle fusion from yeast to man, Nature, 370, 191-193.
  10. Gebauer, F. and Hentze, M.W. (2004) Molecular mechanisms of translational control, Nat Rev Mol Cell Biol, 5, 827-835.
  11. Gingold, H. and Pilpel, Y. (2011) Determinants of translation efficiency and accuracy, Mol Syst Biol, 7, 481.
  12. Holcik, M., et al. (2000) Internal ribosome initiation of translation and the control of cell death, Trends Genet, 16, 469-473.
  13. Ikemura, T. (1985) Codon usage and tRNA content in unicellular and multicellular organisms, Mol Biol Evol, 2, 13-34.
  14. Ingolia, N.T., et al. (2009) Genome-wide analysis in vivo of translation with nucleotide resolution using ribosome profiling, Science, 324, 218-223.
  15. Lucks, J.B., et al. (2008) Genome landscapes and bacteriophage codon usage, PLoS Comput Biol, 4, e1000001.
  16. Mahlab, S., et al. (2012) Conservation of the relative tRNA composition in healthy and cancerous tissues, RNA. 18, 640-652.
  17. Marais, G. and Duret, L. (2001) Synonymous codon usage, accuracy of translation, and gene length in Caenorhabditis elegans, J Mol Evol, 52, 275-280.
  18. Martin, K.C., et al. (2000) Local protein synthesis and its role in synapse-specific plasticity, Curr Opin Neurobiol, 10, 587-592.
  19. Mutch, S.A., et al. (2011) Protein quantification at the single vesicle level reveals that a subset of synaptic vesicle proteins are trafficked with high precision, J Neurosci, 31, 1461-1470.
  20. Nestler, E.J. (2001) Molecular basis of long-term plasticity underlying addiction, Nat Rev Neurosci, 2, 119-128.
  21. Percudani, R. (2001) Restricted wobble rules for eukaryotic genomes, Trends Genet, 17, 133-135.
  22. Pielot, R., et al. (2012) SynProt: A Database for Proteins of Detergent-Resistant Synaptic Protein Preparations, Front Synaptic Neurosci, 4, 1.
  23. Plotkin, J.B. and Kudla, G. (2010) Synonymous but not the same: the causes and consequences of codon bias, Nat Rev Genet, 12, 32-42.
  24. Richter, J.D. and Sonenberg, N. (2005) Regulation of capdependent translation by eIF4E inhibitory proteins, Nature, 433, 477-480.
  25. Ross, C.A. and Poirier, M.A. (2004) Protein aggregation and neurodegenerative disease, Nat Med, 10 Suppl, S10-17.
  26. Sharp, P.M., et al. (1993) Codon usage: mutational bias, translational selection, or both? Biochem Soc Trans, 21, 835-841.
  27. Sudhof, T.C. and Rothman, J.E. (2009) Membrane fusion: grappling with SNARE and SM proteins, Science, 323, 474-477.
  28. Sutton, M.A. and Schuman, E.M. (2006) Dendritic protein synthesis, synaptic plasticity, and memory, Cell, 127, 49-58.
  29. Takamori, S., et al. (2006) Molecular anatomy of a trafficking organelle, Cell, 127, 831-846.
  30. Trimble, W.S., et al. (1991) Cellular and molecular biology of the presynaptic nerve terminal, Annu Rev Neurosci, 14, 93-122.
  31. Tuller, T., et al. (2010) An evolutionarily conserved mechanism for controlling the efficiency of protein translation, Cell, 141, 344-354.
  32. Yanay, C., et al. (2008) Evolution of insect proteomes: insights into synapse organization and synaptic vesicle life cycle, Genome Biol, 9, R27.
  33. Zhang, Z., et al. (2010) Nonsense-mediated decay targets have multiple sequence-related features that can inhibit translation, Mol Syst Biol, 6, 442.
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Paper Citation


in Harvard Style

Mahlab S., Linial I. and Linial M. (2013). Translation Efficiency of Synaptic Proteins and Its Coding Sequence Determinants . In Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013) ISBN 978-989-8565-35-8, pages 151-157. DOI: 10.5220/0004238401510157


in Bibtex Style

@conference{bioinformatics13,
author={Shelly Mahlab and Itai Linial and Michal Linial},
title={Translation Efficiency of Synaptic Proteins and Its Coding Sequence Determinants},
booktitle={Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013)},
year={2013},
pages={151-157},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0004238401510157},
isbn={978-989-8565-35-8},
}


in EndNote Style

TY - CONF
JO - Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms - Volume 1: BIOINFORMATICS, (BIOSTEC 2013)
TI - Translation Efficiency of Synaptic Proteins and Its Coding Sequence Determinants
SN - 978-989-8565-35-8
AU - Mahlab S.
AU - Linial I.
AU - Linial M.
PY - 2013
SP - 151
EP - 157
DO - 10.5220/0004238401510157