RNA as a carrier of epigenetic information

Abstract

Both prokaryotic and eukaryotic cells release into the extracellular matrix membrane-bound structures of different sizes, origin and composition, collectively called extracellular vesicles (EVs) [1]. Tumor cells, in particular, use EVs to transfer both nucleic acids and proteins to the surrounding normal cells, thus inducing 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 remodelling proteases (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 the medium EVs containing a sumoylated form of H1.0 histone and even H1.0 mRNA [5]. By a T1 RNaseprotection assay, we evidenced, in these EVs, three main H1.0 RNA-protein complexes, the most abundant of which had an apparent molecular mass of about 65 kDa. By affinity chromatography on biotinylated H1.0 RNA, we isolated a group of proteins, then analysed by mass spectrometry. One of these proteins is the myelin expression factor-2 (MYEF2). The presence of this protein in EVs was also confirmed by Western blot analysis [5]. MYEF2 was already known as a transcription factor with putative RNA-binding domains. Our demonstration of its actual ability to bind RNA, together with the well accepted ability of EVs to transfer microRNAs (miRNAs) and long non coding RNAs (lncRNAs), rises the possibility that different classes of RNA can function as carriers of factors that, once in receiving cells, epigenetically change their transcriptional potential. [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.