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Extracellular Vesicles (EVs)
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Alice Braga, Giulia Manferrari, Jayden A. Smith, Stefano Pluchino
Another class of small non-coding RNA that has been found to be enriched in EVs are the Y-RNAs (Driedonks and Nolte-’t Hoen 2018). Y-RNAs were first characterized in serum from lupus patients but they have been demonstrated to be highly conserved among vertebrate species, and a homologous structure is also present in nematodes. In humans, four different Y-RNAs have been described, all containing a long stem but differing in their primary and secondary structures (Kowalski and Krude 2015). Y-RNAs are implicated in several crucial cellular functions, such as initiation of chromosomal DNA replication (Gardiner et al. 2009), as well as playing a role in RNA stability and quality control (Stein et al. 2005). EV-trafficked Y-RNAs were first identified in EVs derived from cultured dendritic cells (DCs). Interestingly, host Y-RNAs are encapsulated in the capsids of viruses along with the viral genome, likely enhancing viral assembly, stability, or infectivity (Nolte-’t Hoen et al. 2012). Based on this evidence and on the high amount of Y-RNA observed in EVs, the release of Y-RNA as an evolutionarily conserved mechanism, by which cellular RNAs are stabilized in vesicles allowing functional RNA transfer into target cells, was proposed. Similar enrichment has been observed in EVs derived from different cultured cell types, including breast cancer lines (Tosar et al. 2015) or glioblastoma cells (Wei et al. 2017). Nevertheless, these studies identified only fragments of Y-RNA arms, likely due to technical limitations; Y-RNAs are characterized by complex RNA structures that hamper efficient reverse transcriptases and lead to overestimation of fragments compared to full-length Y-RNAs (Driedonks and Nolte-’t Hoen 2018). A variety of proteins have also been described as interacting with Y-RNAs, with their functions inferred as a consequence. Among these proteins, Y-box binding protein 1 (YBX1) has been found to play a crucial role in the sorting of miR-223 into exosomes (Shurtleff et al. 2016): while miR-223 was found enriched in exosomes derived from HEK293T cells, its packaging was compromised when YBX1 was knocked down, suggesting a role as chaperone-mediating sorter. The density gradient purified vesicle fraction from this work showed the absence of Ago2 protein, confirming and supporting more recent findings from Jeppesen et al. (2019) in redefining the nature of exosomes. While packaged miR-223 was found to be decreased upon deletion of YBX1, YBX1 is also known to interact with other RNA types, suggesting a complexity of RNA trafficking from cells to EVs and the need for a further and deeper characterization of such mechanisms.
MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma
Published in Archives of Environmental & Occupational Health, 2020
Elena Sturchio, Maria Grazia Berardinelli, Priscilla Boccia, Miriam Zanellato, Silvia Gioiosa
Another potential target for mesothelioma treatment strategies, as demonstrated by Johnson et al,42 could be miR-137. Mir-137 exhibits a tumor-suppressive function in MPM by targeting Y-box binding protein 1 (YBX1) whose downregulation determines a reduction of tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 could represent a potential target for novel mesothelioma treatment strategies.