Exploring the RNA landscape of endothelial exosomes

Pérez-Boza, Jennifer; Lion, Michelle; Struman, Ingrid

doi:10.1261/rna.064352.117

Cited by 60 publications

(46 citation statements)

References 89 publications

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“…A number of defined RBPs can be used to recognize and sort RNAs with specific binding motifs into exosomes (67)(68)(69). These specific motifs are shared by RNAs in EVs, which may facilitate their targeting to EVs.…”

Section: Exosomal Circrnas and Their Sorting Mechanismsmentioning

confidence: 99%

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

et al. 2020

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Exosomes are nanoscale phospholipid bilayer vesicles that can be artificially engineered into vectors for the treatment of cancer. Circular RNA (circRNA), a type of non-coding RNA, has crucial regulatory functions in various aspects of cancer, such as tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemo-and radiotherapeutic resistance, as well as in cancer prognosis. Notably, the exosomal transfer of circRNAs may function to both promote and inhibit cancer. Numerous studies have addressed the importance of circRNAs in cancer and non-coding RNAs (such as microRNAs and long non-coding RNAs) in exosomes. However, little research has focussed on a class of RNAs called exosomal circRNAs. The present review discusses current studies regarding exosomal circRNAs, including their biogenesis and biological functions, their abundance in exosomes and possible sorting mechanisms and their potential roles in both promoting and inhibiting cancer. It is predicted that in the next five years there will be increasing research exploring the functional mechanisms of exosomal circRNA in various diseases, in particular their roles in cancer genesis and progression.

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Section: Exosomal Circrnas and Their Sorting Mechanismsmentioning

confidence: 99%

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

et al. 2020

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“…However, there is a mounting consensus in the literature suggesting miRNAs are not the most abundant RNA species in EVs. Rather, fragments of other noncoding RNAs including ribosomal RNA (rRNA), transfer RNA (tRNA) YRNAs, 7S RNA, and Vault RNAs are generally more abundant in EVs than individual miRNAs and their levels in EVs are enriched compared to intracellularly (Chahar, Corsello, Kudlicki, Komaravelli, & Casola, ; Driedonks et al, ; Lässer et al, ; Nolte‐'t Hoen et al, ; Pérez‐Boza, Lion, & Struman, ; Tosar et al, ; Wei et al, ). Although fragmented noncoding RNAs have historically been considered degradation products, in many cases the fragments arise from specific processing events.…”

Section: Looking Beyond Mirnas—ribosomal Rna and Transfer Rna Fragmenmentioning

confidence: 99%

Extracellular RNA in viral–host interactions: Thinking outside the cell

et al. 2019

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Small RNAs and their associated RNA interference (RNAi) pathways underpin diverse mechanisms of gene regulation and genome defense across all three kingdoms of life and are integral to virus–host interactions. In plants, fungi and many animals, an ancestral RNAi pathway exists as a host defense mechanism whereby viral double‐stranded RNA is processed to small RNAs that enable recognition and degradation of the virus. While this antiviral RNAi pathway is not generally thought to be present in mammals, other RNAi mechanisms can influence infection through both viral‐ and host‐derived small RNAs. Furthermore, a burgeoning body of data suggests that small RNAs in mammals can function in a non‐cell autonomous manner to play various roles in cell‐to‐cell communication and disease through their transport in extracellular vesicles. While vesicular small RNAs have not been proposed as an antiviral defense pathway per se, there is increasing evidence that the export of host‐ or viral‐derived RNAs from infected cells can influence various aspects of the infection process. This review discusses the current knowledge of extracellular RNA functions in viral infection and the technical challenges surrounding this field of research. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action

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“…The content of exosomes is dictated by the parent cell type, as well as by the status and the environment of the cells at the time of production [3]. Even though exosomes may carry different cargo (coding and non-coding RNA [4], DNA [5], lipids [6] and proteins [7]), multiple studies have shown that the loading of specific RNAs (in disease) can promote phenotypic changes in the recipient cells [8].…”

Section: Introductionmentioning

confidence: 99%

hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells

Pérez-Boza

Boeckx

Lion

et al. 2020

Cell. Mol. Life Sci.

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The chemotherapeutic drug epirubicin increases the exosomal export of miR-503 in endothelial cells. To understand the mechanisms behind this process, we transfected endothelial cells with miR-503 carrying a biotin tag. Then, we pulled-down the proteins interacting with miR-503 and studied their role in microRNA exosomal export. A total of four different binding partners were identified by mass spectrometry and validated by western blotting and negative controls, among them ANXA2 and hnRNPA2B1. Using knock-down systems combined with pull-down analysis, we determined that epirubicin mediates the export of miR-503 by disrupting the interaction between hnRNPA2B1 and miR-503. Then, both ANXA2 and miR-503 are sorted into exosomes while hnRNPA2B1 is relocated into the nucleus. The combination of these processes culminates in the increased export of miR-503. These results suggest, for the first time, that RNA-binding proteins can negatively regulate the exosomal sorting of microRNAs. Keywords Exosomes • EVs • MicroRNAs • Exosomal export • RNA-binding proteins Abbreviations Epi Epirubicin EVs Extracellular vesicles HUVECs Human umbilical vein endothelial cells HMVECs Human microvascular endothelial cells ANXA2 Annexin A2 hnRNPA2B1 Heteronuclear ribonucleoprotein A2/B1 TSP1/thbs1 Thrombospondin 1 SYN Syntenin VIM Vimentin Vinculin Vinculin MEC MicroRNA exporting complex Cellular and Molecular Life Sciences Jennifer Pérez-Boza and Amandine Boeckx contributed equally to the work.

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Exploring the RNA landscape of endothelial exosomes

Cited by 60 publications

References 89 publications

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

Extracellular RNA in viral–host interactions: Thinking outside the cell

hnRNPA2B1 inhibits the exosomal export of miR-503 in endothelial cells

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