Tiny RNAs and their voyage via extracellular vesicles: Secretion of bacterial small RNA and eukaryotic microRNA

Abstract

MicroRNAs are small non-coding RNAs that bind to the 3′-untranslated region of target mRNAs and have transcriptional or translational inhibitory function in eukaryotes. Before microRNAs were widely known, bacterial non-coding small RNAs around 50–200 nt in length were discovered whose mechanism of action resembled that of microRNAs. Recently, RNAs that are of similar size to or smaller than microRNAs have been discovered in bacteria and indeed, this class of small RNAs have been found throughout all domains of life. Moreover, recent findings suggest that these tiny RNAs can be released via extracellular vesicles (such as exosomes in eukaryotes and outer membrane vesicles in bacteria), which in turn heralds a new field of research, interkingdom communication. This review discusses two similar classes of small RNAs in evolutionarily distinct eukaryotes and bacteria. In addition to their biogenesis and regulation, we discuss small RNA vehicles and their secretion. Impact statement The possible endogenous functions of small RNAs such as regulatory small RNAs in bacteria and microRNAs in eukaryotes have been extensively studied since they were first discovered. However, their powerful functions should not be seen as limited to their cells of origin. Recently, several papers have demonstrated that small RNAs function as signaling molecules between cells. This is possible because small RNAs can be shuttled around after being incorporated into environmentally protective extracellular vesicles. It is now clearly plausible that secreted small RNAs can regulate other types of cells through biofluids. Given their “common molecule” status, the role of small RNAs in mediating bacteria-human crosstalk is an emerging and competitive area of genetic research. This review provides insight into the function of small RNAs in intercellular and even interkingdom communication.

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

“…Eukaryotic cells' EVs originate from the process of plasma membrane budding or fusion of multivesicular endosomes with the plasma membrane. Relatively, EVs derived from Gram-positive and Gram-negative bacteria may disperse in extracellular space by outward budding of the prokaryotic membrane [10][11][12]. In past reviews, the EVs tend to be divided into three main subsets known as exosomes, microvesicles (MVs), and apoptotic bodies [13,14].…”

The roles of small RNAs: insights from bacterial quorum sensing

“…In addition to that, discovery of quorum regulatory RNAs (Qrr) [30,61], demonstrated sRNA can regulate interkingdom communication. Yet it is not going to be discussed in detail as a directly related communication is arising over the last years [62][63][64][65]. Extracellular vesicles (EVs) were initially thought to only exist in eukaryotes [66] and play a critical role in intercellular communication by carrying RNA and proteins [62,67,68].…”

“…Extracellular vesicles (EVs) were initially thought to only exist in eukaryotes [66] and play a critical role in intercellular communication by carrying RNA and proteins [62,67,68]. It has also been described that EVs can carry miRNAs and aid in their horizontal transfer [67][68][69][70] and that sRNA may be secreted extracellularly by similar means in prokaryotes [63,69,[71][72][73][74]. EVs in prokaryotes are named outer membrane microvesicles (OMVs) [62] since they are released from the outer membrane [75].…”

The role of gene sculptor microRNAs in human precancerous lesions

“… 27 Insulin receptor substrate 1 is an insulin-like growth factor 1 receptor or scaffolding protein of the insulin receptor, which can enhance the signals of these receptor pathways. 28 Cancer cells and secretory miRNAs generated by cells in the tumor microenvironment regulate metabolic pathways and promote survival and metastasis in autocrine, paracrine, and endocrine patterns. 29 …”