Di Liegro Carlo Maria, Schiera Gabriella, Di Liegro Italia
Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo (UNIPA), I-90128 Palermo, Italy.
Department of Experimental Biomedicine and Clinical Neurosciences (BIONEC), University of Palermo,I-90127 Palermo,Italy.
Genes (Basel). 2017 Sep 22;8(10):240. doi: 10.3390/genes8100240.
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally transfer molecules, and hence properties, to neighboring cells. By interacting with proteins that are specifically sorted to EVs, mRNAs as well as ncRNAs can be transferred from cell to cell. In this review, we discuss the mechanisms underlying the sorting to EVs of different classes of molecules, as well as the role of extracellular RNAs and the associated proteins in altering gene expression in the recipient cells. Importantly, if, on the one hand, RBPs play a critical role in transferring RNAs through EVs, RNA itself could, on the other hand, function as a carrier to transfer proteins (i.e., chromatin modifiers, and transcription factors) that, once transferred, can alter the cell's epigenome.
信使核糖核酸（mRNA）代谢和亚细胞定位的转录后调控在发育过程和细胞分化过程中都至关重要。mRNA除了携带遗传信息外，还包含顺式作用信号（邮政编码），通常存在于其5'和3'非翻译区（UTR）。通过与这些信号结合，反式作用因子，如RNA结合蛋白（RBP）和/或非编码RNA（ncRNA），控制mRNA的定位、翻译和稳定性。RBP还可以与不同大小的非编码RNA形成复合物。细胞外囊泡（EV）的释放是一个保守过程，它使正常细胞和癌细胞都能将分子及其特性水平转移到邻近细胞。通过与特异性分选到EV的蛋白质相互作用，mRNA以及ncRNA可以在细胞间转移。在这篇综述中，我们讨论了不同类分子分选到EV的潜在机制，以及细胞外RNA和相关蛋白质在改变受体细胞基因表达中的作用。重要的是，如果一方面RBP在通过EV转移RNA中起关键作用，那么另一方面RNA本身可以作为载体转移蛋白质（即染色质修饰剂和转录因子），这些蛋白质一旦转移，就可以改变细胞的表观基因组。
