Abstract

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained within EVs have been considered as candidate interspecies-communication molecules, due to their demonstrated capacity to modulate gene expression in multiple cell types and species. While research into this field is in its infancy, elucidating the mechanisms that underlie host–microbe interactions and communications promises to impact many fields of biological research, including human health and medicine. Thus, this review discussed the results of recent studies that have examined the ways in which EVs and sRNAs mediate ‘microbe–host’ and ‘host–microbe’ interspecies communication.

Highlights

  • Extracellular RNAs encompass secreted RNAs that are thought to be mainly encased within extracellular vesicles (EVs) or are otherwise tightly bound to cellular proteins and lipids [1]

  • The majority of EV RNA content comprises small RNAs, such as microRNAs, and miRNA-sized sRNAs [3,4]. These have recently gained attention due to their proposed gene-regulatory roles [2]; for example, miRNAs contained in EVs have been recently suggested as biomarkers for cancer and other diseases [5,6]. miRNAs are initially processed from precursor miRNAs, before being processed to their final mature form by the RNase-III enzyme, Dicer [7,8]

  • Of the many sRNA-mediated host–microbe interactions reported to date, this review focuses on the recently identified role of Extracellular RNAs (exRNAs) in facilitating mutual communication between microbes and hosts

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Summary

Introduction

Extracellular RNAs (exRNAs) encompass secreted RNAs that are thought to be mainly encased within extracellular vesicles (EVs) or are otherwise tightly bound to cellular proteins and lipids [1]. Of the many sRNA-mediated host–microbe interactions reported to date, this review focuses on the recently identified role of exRNAs in facilitating mutual communication between microbes and hosts Perhaps due to their limited space and/or special selection mechanisms, transfer RNA (tRNA) fragments and miRNAs have been found to occur more frequently in exosomes than other sRNAs, such as messenger RNAs (mRNAs) and ribosomal RNAs (rRNAs) [25,26]. Bacterial EV biogenesis mechanisms have been suggested to be species-specific, and likely related to the physical structure the of the cell-wall peptidoglycan layer, and/or its LPS or membrane transporter-protein composition (see [15,35] for more details) This is because in gram-negative bacteria, the outer membrane must detach from beneath the peptidoglycan layer, form a vesicular shape, and undergo fission to form an EV. SRNA, small RNA; T cells, thymus cells; OMV, outer membrane vesicle; IL, interleukin; JAK-STAT, Janus kinase/signal transducers and activators of transcription; HeLa, Henrietta Lacks cell line; miRNA, micro-RNAs; RISC, RNA-induced silencing complex; THP-1, human monocytic cell line

Regulation of Host Genes by sRNAs Contained within Bacterial EVs
Regulation of Bacterial Genes by sRNAs in Host EVs
Concluding Remarks
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