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Extracellular Vesicles for Nucleic Acid Delivery
Published in Yashwant Pathak, Gene Delivery, 2022
Md Meraj Anjum, Dulla Naveen Kumar, Aiswarya Chaudhuri, Sanjay Singh, Ashish Kumar Agrawal
Apart from proteins and lipids, EVs are also comprised of RNA species. The EVs derived from mammalian cells are extensively scrutinized for the availability of RNA species, provided with latest methods of sequencing. The RNA includes messenger RNAs, non-coding RNAs, microRNA, transfer RNA, ribosomal RNA, small nuclear RNA, small nucleolar RNA, small cytoplasmic RNA, Y-RNA, and vault RNA [55]. Apart from RNAs, the mammalian EVs are also comprised of certain degraded products. However, the relative availability of various RNAs vary between donor cells and extravesicular cells. For instance, EVs derived from dendritic cells showed enhanced levels of vault RNA, SRPRNA, and Y-RNA as compared to the parent cells [73]. Overexpressed cellular miRNAs, like miR92a-1 and let-7b, were found to be in low concentrations in EVs, while highly expressed EV derived miRNAs, like miR-223, miR-142, and miR-93, were expressed at a lesser concentration in the parent cells. Such an instance implies that RNAs are sorted selectively into the extracellular vesicles during their biosynthesis. Nevertheless, the bacterial OMVs showed a smaller amount of expressed RNAs. It has been observed that the huge range of RNAs, like transfer RNA, transfer-messenger RNAs, ribosomal RNA, signal recognition particle-RNA, and 6S RNA, were found in EVs released from bacteria [62]. These findings are somewhat similar to the finding obtained from that of extracellular vesicles released from the mammalian cell, where the distinctive sorting of distinct RNAs has been unveiled. The detailed summary of protein, lipid components, and RNAs found in exosomes is given in Table 3.2.
How does an RNA selfie work? EV-associated RNA in innate immunity as self or danger
Published in Journal of Extracellular Vesicles, 2020
Yu Xiao, Tom Driedonks, Kenneth W. Witwer, Qian Wang, Hang Yin
The molecular context of RNA could be another means to distinguish “danger” from normal RNA. As an example, the signal recognition particle RNA RN7SL1, an endogenous RNA normally shielded by RNA-binding protein SRP9/14, was upregulated in activated stromal cells in the context of breast cancer [14]. At these abnormal levels, not all copies of RN7SL1 could be bound by the usual protein partner, and the RNA was exported in EVs as naked (or “unshielded”) RNA with an exposed 5’-ppp triphosphate motif. Upon transfer to recipient breast cancer cells, this unshielded 5’-ppp on RN7SL1 activated the cytoplasmic RNA sensor RIG-I, thus promoting cancer aggression phenotypes (Figure 1). Note that a previous report found EVs to be enriched with 5’-ppp miRNAs [15]. What remains unclear is how the carrier EVs fused and delivered the unshielded cargo, as well as the level of transfer required to achieve these effects in vivo. In another example, Polymerase III-transcribed cellular RNA, in particular Y-RNA, was also shown to bind RIG-I via a triphosphate motif [16]. This was counteracted by the cellular triphosphatase Dusp11, which prevents unwarranted RNA sensing in healthy cells [16]. Whether Dusp11 is also involved in reducing RNA sensing of EV-transferred RNA cargo remains to be investigated.
Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes
Published in Journal of Extracellular Vesicles, 2018
Ryan C. Middleton, Russell G. Rogers, Geoffrey De Couto, Eleni Tseliou, Kristin Luther, Ronald Holewinski, Daniel Soetkamp, Jennifer E. Van Eyk, Travis J. Antes, Eduardo Marbán
Next, A1-EV RNA cargo was profiled by RNA-Seq and mapped using sequence similarity to human genome databases. We identified a high proportion of antisense and coding messenger RNA sequences, as well as abundant lincRNA sequences (Figure 8(a)), but a very low relative abundance of miRNAs (0.014%). The largest proportion of identified RNAs (34.4%) mapped to non-coding RNA (rfam [51]) with the most abundant species belonging to the Signal Recognition Particle RNA family, universally conserved ribonucleoprotein complexes involved in protein trafficking [52].