Extracellular vesicles shed by melanoma cells contain a modified form of H1.0 linker histone and H1.0 mRNA-binding proteins

Abstract

Extracellular vesicles (EVs) are now recognized as a fundamental way for cell-to-cell horizontal transfer of properties, in both physiological and pathological conditions. Most of EV-mediated cross-talk among cells depend on the exchange of proteins, and nucleic acids, among which mRNAs, and non-coding RNAs such as different species of miRNAs. Cancer cells, in particular, use EVs to discard molecules which could be dangerous to them (for example differentiation-inducing proteins such as histone H1.0, or antitumor drugs), to transfer molecules which, after entering the surrounding cells, are able to transform their phenotype, and even to secrete factors, which allow escaping from immune surveillance. Herein we report that melanoma cells not only secrete EVs which contain a modified form of H1.0 histone, but also transport the corresponding mRNA. Given the already known role in tumorigenesis of some RNA binding proteins (RBPs), we also searched for proteins of this class in EVs. This study revealed the presence in A375 melanoma cells of at least three RBPs, with apparent MW of about 65, 45 and 38 kDa, which are able to bind H1.0 mRNA. Moreover, we purified one of these proteins, which by MALDI-TOF mass spectrometry was identified as the already known transcription factor MYEF2.

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

“…Together with these different classes of RNA, EVs also contain RNA-binding proteins (RBPs) [160,161]. Given the known role of these latter proteins in the sub-cellular RNA localization, it has been suggested that during vesicle biogenesis RBPs can regulate accumulation of selected RNAs into vesicles [161][162][163].…”

“…Loss of the lysosomal kinesin adaptor ADP-ribosylation factor-like protein 8 (Arl8) causes accumulation of both synaptic vesicles and AZ-protein-containing vesicles in the neuronal body, with the consequent alteration of the presynaptic structures and impairment of neurotransmission [168]. Super-resolution microscopy and live imaging have also Together with these different classes of RNA, EVs also contain RNA-binding proteins (RBPs) [160,161]. Given the known role of these latter proteins in the sub-cellular RNA localization, it has been suggested that during vesicle biogenesis RBPs can regulate accumulation of selected RNAs into vesicles [161][162][163].…”

Assessment of Extracellular Vesicles Purity Using Proteomic Standards

“…23–25 These proteins were included because transferrin is a typical abundant serum protein, apoE was reported as an EVs-associated regulatory protein, 26 and there are reports supporting the presence of histones in EVs. 27,28 The data in pmol of targeted protein per mg of the total protein in EVs(208K) and EVs(SEC) representative preparations are shown in Figure 3. Since the dynamic range of targeted proteins is approximately 10 5 , the data for a representative experiment are shown in two separate groups with different y -axis scales.…”

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

“…RBP also account for localization and trafficking of RNA-protein complexes in cells (115,116). Finally, the mRNA profile of Exo differs from that of cells (117), metabolic enzymes and proteins engaged in cell-cell and cell-matrix adhesion being frequently overrepresented (118)(119)(120), and possibly translated in Exo (121,122).…”