The Long and Short of It: The Emerging Roles of Non-Coding RNA in Small Extracellular Vesicles

Small extracellular vesicles (EVs) play a significant role in intercellular communication through their non-coding RNA (ncRNA) cargo. While the initial examination of EV cargo identified both mRNA and miRNA, later studies revealed a wealth of other types of EV-related non-randomly packed ncRNAs, including tRNA and tRNA fragments, Y RNA, piRNA, rRNA, and lncRNA. A number of potential roles for these ncRNA species were suggested, with strong evidence provided in some cases, whereas the role for other ncRNA is more speculative. For example, long non-coding RNA might be used as a potential diagnostic tool but might also mediate resistance to certain cancer-specific chemotherapy agents. piRNAs, on the other hand, have a significant role in genome integrity, however, no role has yet been defined for the piRNAs found in EVs. While our knowledgebase for the function of ncRNA-containing EVs is still modest, the potential role that these EV-ensconced ncRNA might play is promising. This review summarizes the ncRNA content of EVs and describes the function where known, or the potential utility of EVs that harbor specific types of ncRNA.