22:T4ca,Cardiosphere-derived cells (CDCs) reduce myocardial infarct size via secreted extracellular vesicles (CDC-EVs), including exosomes, which alter macrophage polarization. We questioned whether short non-coding RNA species of unknown function within CDC-EVs contribute to cardioprotection. The most abundant RNA species in CDC-EVs is a Y RNA fragment (EV-YF1); its relative abundance in CDC-EVs correlates with CDC potency in vivo Fluorescently labeled EV-YF1 is actively transferred from CDCs to target macrophages via CDC-EVs. Direct transfection of macrophages with EV-YF1 induced transcription and secretion of IL-10. When cocultured with rat cardiomyocytes, EV-YF1-primed macrophages were potently cytoprotective toward oxidatively stressed cardiomyocytes through induction of IL-10. In vivo, intracoronary injection of EV-YF1 following ischemia/reperfusion reduced infarct size. A fragment of Y RNA, highly enriched in CDC-EVs, alters Il10 gene expression and enhances IL-10 protein secretion. The demonstration that EV-YF1 confers cardioprotection highlights the potential importance of diverse exosomal contents of unknown function, above and beyond the usual suspects (e.g., microRNAs and proteins).23:T508,The RNA polypyrimidine tract-binding protein PTBP3 is a little studied paralog of PTBP1, which has oncogenic properties. In this study, we demonstrate that PTBP3 induces epithelial-mesenchymal transition (EMT) in breast tumor cells and promotes their invasive growth and metastasis. Elevated expression of PTBP3 associated significantly with lymph node metastasis, advanced histology grade, TNM stage, and poor 5-year overall survival of patients. In human mammary epithelial cells, PTBP3 overexpression was sufficient to induce EMT and to enhance cell migration, invasion, and cancer stem-like cell properties. PTBP3 regulated expression of the EMT regulatory transcription factor ZEB1 by binding the 3'UTR of its mRNA, thereby preventing its degradation. Conversely, ZEB1 ablation blocked the ability of PTBP3 to induce EMT. Overall, our findings define PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they establish an oncogenic function of PTBP3, suggesting its candidacy as a theranostic target.Significance: These findings define PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they establish an oncogenic function of PTBP3, suggesting its candidacy as a theranostic target. Cancer Res; 78(2); 387-98. ©2017 AACR.24:T541,By screening a yeast two-hybrid library with COOH-terminal fragments of vinculin/metavinculin as the bait, we identified a new protein termed raver1. Raver1 is an 80-kD multidomain protein and widely expressed but to varying amounts in different cell lines. In situ and in vitro, raver1 forms complexes with the microfilament-associated proteins vinculin, metavinculin, and alpha-actinin and colocalizes with vinculin/metavinculin and alpha-actinin at microfilament attachment sites, such as cell-cell and cell matrix contacts of epithelial cells and fibroblasts, respectively, and in costameres of skeletal muscle. The NH2-terminal part of raver1 contains three RNA recognition motifs with homology to members of the heterogeneous nuclear RNP (hnRNP) family. Raver1 colocalizes with polypyrimidine tract binding protein (PTB)/hnRNPI, a protein involved in RNA splicing of microfilament proteins, in the perinucleolar compartment and forms complexes with PTB/hnRNPI. Hence, raver1 is a dual compartment protein, which is consistent with the presence of nuclear location signal and nuclear export sequence motifs in its sequence. During muscle differentiation, raver1 migrates from the nucleus to the costamere. We propose that raver1 may coordinate RNA processing and targeting as required for microfilament anchoring in specific adhesion sites.

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