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

Abstract

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.

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

“…Since caspase-3 is classically regarded as an "executioner" caspase [138,139] EVs are associated with a rich diversity of cargo which includes various non-coding RNAs (i.e. small non-coding and long non-coding RNAs), as described elsewhere [140,141,142,143,144,145]. Mechanistically speaking, this cargo is expected to drive the functional effects that are attributed to EVs.…”

Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions

“…An interesting class of miRNAs includes "circulating miRNAs" characterized by their active release through EVs or passive release upon cell death [12,30,[65][66][67][68][69]. Several studies have shown that miRNAs can be identified in a variety of body fluids, including plasma, saliva, urine, seminal fluids, breast milk, cerebrospinal fluid and more recently also in feces, leading to the definition of circulating miRNAs [70][71][72][73][74].…”

“…Circulating miRNAs have been found associated with EVs, with high-density lipoproteins or with proteins involved in their processing such as the argonaute protein. EVs form includes microvesicles and exosomes that represent the common form of released extracellular miRNAs [30,65,68,69]. Nevertheless, miRNAs show the features of an ideal biomarker being available in body fluids, tissue-and disease-specificities, extremely stable and easily collected and detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) [40,[76][77][78][79].…”

Reflections on the Role of Malat1 in Gynecological Cancer

“…However, the clinical use of exosomes as biomarkers is limited by the extensive processing time required to isolate and detect exosomes. 82 Fortunately, researchers are now working on micro-and nano-technologies in an attempt to overcome these technical challenges. 83 The potential clinical use of Malat1 is also supported by rapid developments in medical biotechnology.…”