RNA as a carrier of epigenetic information

Both prokaryotic and eukaryotic cells release into the extracellular matrix membrane-boundstructures of different sizes, origin and composition, collectively called extracellular vesicles (EVs) [1]. Tumorcells, in particular, use EVs to transfer both nucleic acids and proteins to the surrounding normal cells, thusinducing in them transformed behaviours or killing them. G26/24 oligodendroglioma cells, for example,transfer by EVs pro-apoptotic proteins, such as TRAIL and Fas-Ligand [2], extracellular matrix remodellingproteases (such as ADAMTS) [3], and even the H1.0 histone protein [4].Another tumour cell line, with a different tissue origin (A375 melanoma cells) releases into themedium EVs containing a sumoylated form of H1.0 histone and even H1.0 mRNA [5]. By a T1 RNaseprotectionassay, we evidenced, in these EVs, three main H1.0 RNA-protein complexes, the most abundantof which had an apparent molecular mass of about 65 kDa. By affinity chromatography on biotinylated H1.0RNA, we isolated a group of proteins, then analysed by mass spectrometry. One of these proteins is themyelin expression factor-2 (MYEF2). The presence of this protein in EVs was also confirmed by Western blotanalysis [5]. MYEF2 was already known as a transcription factor with putative RNA-binding domains. Ourdemonstration of its actual ability to bind RNA, together with the well accepted ability of EVs to transfermicroRNAs (miRNAs) and long non coding RNAs (lncRNAs), rises the possibility that different classes of RNAcan function as carriers of factors that, once in receiving cells, epigenetically change their transcriptionalpotential.[1] Schiera G, et al. 2015. Biomed Res Int. 2015:152926.[2] Lo Cicero A et al. 2011, Int J Oncol 39:1353-7[3] Lo Cicero A et al. 2012, Matrix Biol 31:229-33[4] Schiera G et al. 2013, Int J Oncol 43:1771-6[5] Schiera G. et al. 2016. Int J Oncol. 49:1807-1814.