How does an RNA selfie work? EV‐associated RNA in innate immunity as self or danger

Abstract

Innate immunity is a first line of defence against danger. Exogenous pathogen-or microbeassociated molecular patterns (PAMPs or MAMPs) trigger innate immune responses through wellunderstood cellular pathways. In contrast, endogenous damage-associated molecular patterns (DAMPs) convey "danger signals" via their (mis)localization or modification. Both MAMPs and DAMPs are often communicated on or within extracellular vesicles (EVs). Despite growing evidence for the importance of EVs and their cargo in modulating innate immune responses, in some cases, it is unclear how EV-transported molecules are sensed as abnormal. In particular, EVs constitutively carry RNA, which is also abundant in the cytoplasm. How, then, would RNA convey a danger signal as a cargo of EVs? In this Perspective, we offer some thoughts on how EVassociated RNAs might raise the alarm for innate immune responses-or silence them.

Extracellular vesicle IL-32 promotes the M2 macrophage polarization and metastasis of esophageal squamous cell carcinoma via FAK/STAT3 pathway

“…EV are an important mediator for intercellular communication [ 46 ]. In recent years, spatial regulation between tumor cells and stromal cells by means of EV to mediate the immune escape, drug resistance and tumorigenesis was a provocative topic [ 47 , 48 ].…”

The Role of Nucleases and Nucleic Acid Editing Enzymes in the Regulation of Self-Nucleic Acid Sensing

“…Several studies have also shown that cell-free miRNA is particularly resistant to nucleases (66), due to its association to proteins rather than with vesicles, indicating multiple methods of cfRNA stabilization may exist. The immunostimulatory capacity of circulatory MP-associated RNA has been investigated to some degree in the context of RNA specific TLR activation; however this as well as the role of MP-free circulating RNA species remain active areas of research (67,68).…”

Theragnostic Applications of Mammal and Plant-Derived Extracellular Vesicles: Latest Findings, Current Technologies, and Prospects

“…EVs are heterogeneous sacs of membranous vesicles released from the cells into the surrounding environment [9]. The recognized role of EVs is to carry a molecular cargo including RNA and surface markers [10] originating from the mother cell and reflect their status [11] to be delivered to the receiving cells. Organisms that range from prokaryotic cells to higher eukaryotes can produce EVs.…”

“…1 Endosomal sorting complex required for transport, 2 Rab-associated binding, 3 Heat shock protein 5, 4 Gelsoline , 5 Fascin actin-bundling protein 1 , 6 Adenosine triphosphatase protein, 7 Rho-associated kinase, 8 Annexin A1, 9 coronin actin protein, 10 ADP-ribosylation factor 1, 11 Annexin A6, 12 Lck/Yes novel tyrosine kinase, 13 oxytocin receptor, 14 Syntaxin 4, 15 Guanine nucleotide-binding protein, 16 Actin gamma 1, 17 Destrin, 18 Filamin A, 19 Coactosin-like protein 1, 20 Keratin 1,9 and 10, 21 Moesin, 22 Profilin 1, 23 DW repeat domain 1, 24 Tumor susceptibility gene 101, 25 Lysosomal-associated membrane protein 1, 26 Flotillin-1, 27 Prion protein, 28 ALG-2interacting protein X, 29 Vacuolar protein sorting 4, 30 Heat shock protein70.…”