Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA

BACKGROUND: Exosomes are small extracellular nanovesicles of endocytic origin that mediate different signals between cells, by surface interactions and by shuttling functional RNA from one cell to another. Exosomes are released by many cells including mast cells, dendritic cells, macrophages, epithelial cells and tumour cells. Exosomes differ compared to their donor cells, not only in size, but also in their RNA, protein and lipid composition. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that exosomes, released by mouse mast cells exposed to oxidative stress, differ in their mRNA content. Also, we show that these exosomes can influence the response of other cells to oxidative stress by providing recipient cells with a resistance against oxidative stress, observed as an attenuated loss of cell viability. Furthermore, Affymetrix microarray analysis revealed that the exosomal mRNA content not only differs between exosomes and donor cells, but also between exosomes derived from cells grown under different conditions; oxidative stress and normal conditions. Finally, we also show that exposure to UV-light affects the biological functions associated with exosomes released under oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results argue that the exosomal shuttle of RNA is involved in cell-to-cell communication, by influencing the response of recipient cells to an external stress stimulus

Reverse engineering systems models of regulation: Discovery, prediction and mechanisms

Biological systems can now be understood in comprehensive and quantitative detail using systems biology approaches. Putative genome-scale models can be built rapidly based upon biological inventories and strategic system-wide molecular measurements. Current models combine statistical associations, causative abstractions, and known molecular mechanisms to explain and predict quantitative and complex phenotypes. This top-down 'reverse engineering' approach generates useful organism-scale models despite noise and incompleteness in data and knowledge. Here we review and discuss the reverse engineering of biological systems using top-down data-driven approaches, in order to improve discovery, hypothesis generation, and the inference of biological properties. © 2011 Elsevier Ltd

Cytoplasmic mRNA surveillance pathways

International audienceDuring mRNA synthesis and maturation, the introduction of errors can strongly influence the expression of certain genes and/or the activity of the proteins for which they encode. To minimise these defects, eukaryotic cells have evolved several cytoplasmic and translation-dependent quality control pathways aimed at detecting and degrading mRNAs that would lead to the production of aberrant proteins. The nonsense-mediated mRNA decay pathway (NMD) clears cells from mRNAs harbouring premature in-frame stop codons. Two other pathways (NSD for nonstop decay and NGD for No-Go decay) degrade mRNAs on which ribosomes have stalled during elongation. In this chapter, we describe the current knowledge on the biological roles and molecular mechanisms of these surveillance pathways, which were mainly unravelled using baker’s yeast as model system