Unpacking extracellular vesicles: RNA cargo loading and function

Dellar, Elizabeth R.; Hill, Claire; Melling, Genevieve E; Carter, David R. F.; Baena‐López, Luis Alberto

doi:10.1002/jex2.40

Cited by 36 publications

(39 citation statements)

References 188 publications

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“…In addition, when we compared the cellular RNA with the transcripts identified in the EVs. For C. auris , as shown in other studies in distinct organisms and cell types, the most abundant cellular transcripts were not necessarily identified in the EVs, suggesting an active mechanism of EV cargo selection [ 41 , 42 , 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 76%

Caspofungin Affects Extracellular Vesicle Production and Cargo in Candida auris

Amatuzzi

Zamith-Miranda

Rocha

et al. 2022

JoF

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Antifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, Candida auris stands out for commonly being highly resistant to antifungal drugs, and some isolates are pan-resistant. The rate of mortality linked to C. auris infections varies from 28% to 78%. In this study, we characterized C. auris extracellular vesicles (EVs) in the presence of caspofungin, an echinocandin, which is the recommended first line antifungal for the treatment of infections due to this emerging pathogen. Furthermore, we also analyzed the protein and RNA content of EVs generated by C. auris cultivated with or without treatment with caspofungin. We observed that caspofungin led to the increased production of EVs, and treatment also altered the type and quantity of RNA molecules and proteins enclosed in the EVs. There were distinct classes of RNAs in the EVs with ncRNAs being the most identified molecules, and tRNA-fragments (tRFs) were abundant in each of the strains studied. We also identified anti-sense RNAs, varying from 21 to 55 nt in length. The differentially abundant mRNAs detected in EVs isolated from yeast subjected to caspofungin treatment were related to translation, nucleosome core and cell wall. The differentially regulated proteins identified in the EVs produced during caspofungin treatment were consistent with the results observed with the RNAs, with the enriched terms being related to translation and cell wall. Our study adds new information on how an echinocandin can affect the EV pathway, which is associated with the yeast cell being able to evade treatment and persist in the host. The ability of C. auris to efficiently alter the composition of EVs may represent a mechanism for the fungus to mitigate the effects of antifungal agents.

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Section: Discussionmentioning

confidence: 76%

Caspofungin Affects Extracellular Vesicle Production and Cargo in Candida auris

Amatuzzi

Zamith-Miranda

Rocha

et al. 2022

JoF

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“…To date, both small and total RNA sequencing have considerably advanced our understanding of the diverse EV RNA cargo (reviewed by Dellar et al. (2022)). The present study does not provide any information on EV RNA relative to the parental cell RNA, and therefore, it is not possible to assess whether EV RNAs are enriched in EVs or simply reflect gene expression changes in M1 and M2‐polarized macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Analysing bulk EV RNA precludes the appreciation of the heterogeneity in the transcriptome of single EVs; detection of individual RNAs on a single EV basis, e.g., by flow cytometry, could be employed to study immune cell EV RNA cargo at a more granular level. To date, both small and total RNA sequencing have considerably advanced our understanding of the diverse EV RNA cargo (reviewed by Dellar et al (2022)). The present study does not provide any information on EV RNA relative to the parental cell RNA, and therefore, it is not possible to assess whether EV RNAs are enriched in EVs or simply reflect gene expression changes in M1 and M2-polarized macrophages.…”

Section:  Discussionmentioning

confidence: 99%

Distinct non‐coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

Pantazi

Clements

Abrahams

et al. 2022

J of Extracellular Vesicle

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Macrophages are important antigen presenting cells which can release extracellular vesicles (EVs) carrying functional cargo including non‐coding RNAs. Macrophages can be broadly classified into M1 ‘classical’ and M2 ‘alternatively‐activated’ macrophages. M1 macrophages have been linked with inflammation‐associated pathologies, whereas a switch towards an M2 phenotype indicates resolution of inflammation and tissue regeneration. Here, we provide the first comprehensive analysis of the small RNA cargo of EVs from human M1 and M2 primary macrophages. Using small RNA sequencing, we identified several types of small non‐coding RNAs in M1 and M2 macrophage EVs including miRNAs, isomiRs, tRNA fragments, piRNA, snRNA, snoRNA and Y‐RNA fragments. Distinct differences were observed between M1 and M2 EVs, with higher relative abundance of miRNAs, and lower abundance of tRNA fragments in M1 compared to M2 EVs. MicroRNA‐target enrichment analysis identified several gene targets involved in gene expression and inflammatory signalling pathways. EVs were also enriched in tRNA fragments, primarily originating from the 5′ end or the internal region of the full length tRNAs, many of which were differentially abundant in M1 and M2 EVs. Similarly, several other small non‐coding RNAs, namely snRNAs, snoRNAs and Y‐RNA fragments, were differentially enriched in M1 and M2 EVs; we discuss their putative roles in macrophage EVs. In conclusion, we show that M1 and M2 macrophages release EVs with distinct RNA cargo, which has the potential to contribute to the unique effect of these cell subsets on their microenvironment.

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Section: Discussionmentioning

confidence: 99%

Distinct non-coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

Pantazi

Clements

Abrahams

et al. 2022

Preprint

View full text Add to dashboard Cite

Macrophages are important antigen presenting cells which can release extracellular vesicles (EVs) carrying functional cargo including non-coding RNAs. Macrophages can be broadly classified into M1 'classical' and M2 'alternatively-activated' macrophages. M1 macrophages have been linked with inflammation-associated pathologies, whereas a switch towards an M2 phenotype indicates resolution of inflammation and tissue regeneration. Here, we provide the first comprehensive analysis of the small RNA cargo of EVs from human M1 and M2 primary macrophages. Using small RNA sequencing, we identified several types of small non-coding RNAs in M1 and M2 macrophage EVs including miRNAs, isomiRs, tRNA fragments, piRNA, snRNA, snoRNA and Y-RNA fragments. Distinct differences were observed between M1 and M2 EVs, with higher relative abundance of miRNAs, and lower abundance of tRNA fragments in M1 compared to M2 EVs. MicroRNA-target enrichment analysis identified several gene targets involved in gene expression and inflammatory signalling pathways. EVs were also enriched in tRNA fragments, primarily originating from the 5' end or the internal region of the full length tRNAs, many of which were differentially abundant in M1 and M2 EVs. Similarly, several other small non-coding RNAs, namely piRNAs, snRNAs, snoRNAs and Y-RNA fragments, were differentially enriched in M1 and M2 EVs; we discuss their putative roles in macrophage EVs. In conclusion, we show that M1 and M2 macrophages release EVs with distinct RNA cargo, which has the potential to contribute to the unique effect of these cell subsets on their microenvironment.

show abstract

Unpacking extracellular vesicles: RNA cargo loading and function

Cited by 36 publications

References 188 publications

Caspofungin Affects Extracellular Vesicle Production and Cargo in Candida auris

Caspofungin Affects Extracellular Vesicle Production and Cargo in Candida auris

Distinct non‐coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

Distinct non-coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

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