Potential mechanisms of microRNA mobility

Abstract

microRNAs (miRNAs) are important epigenetic modulators of gene expression that control cellular physiology as well as tissue homeostasis, and development. In addition to the temporal aspects of miRNA-mediated gene regulation, the intracellular localization of miRNA is crucial for its silencing activity. Recent studies indicated that miRNA is even translocated between cells via gap junctional cell-cell contacts, allowing spatiotemporal modulation of gene expression within multicellular systems. Although non coding RNA remains a focus of intense research, studies regarding the intra-and intercellular mobility of small RNAs are still largely missing. Emerging data from experimental and computational work suggest the involvement of transport mechanisms governing proper localization of miRNA in single cells and cellular syncytia. Based on these data, we discuss a model of miRNA translocation that could help to address the spatial aspects of miRNA function and the impact of miRNA molecules on the intercellular signaling network.

Changes in circulating microRNA and arterial stiffness following high‐intensity interval and moderate intensity continuous exercise

“…Secondly, cells may be releasing ci‐miRs as a method of intercellular paracrine or endocrine communication in order to induce responses in target cells. There is substantial evidence supporting the transport of biologically active ci‐miRs between endothelial cells and from endothelial to vascular smooth muscle cells (Bär, Thum, & Gonzalo‐Calvo, 2019; Hergenreider et al., 2012; Jansen et al., 2013, 2015, 2017; Lemcke & David, 2018; Njock & Fish, 2017; Zhou et al., 2013). Either of these mechanisms could explain how ci‐miRs mediate adaptations to exercise training, due to either repeated offloading or transport with acute exercise bouts.…”

Localization of RNAi Machinery to Axonal Branch Points and Growth Cones Is Facilitated by Mitochondria and Is Disrupted in ALS

“…In the developing axonal growth cone, miRNAs modulate axon growth and guidance in response to extrinsic cues by locally regulating protein translation (Holt and Schuman, 2013 ). The mechanism underlying miRNA transport and localization has remained elusive for many years (Kosik, 2006 ; Lemcke and David, 2018 ).…”

Hypoxic Melanoma Cells Deliver microRNAs to Dendritic Cells and Cytotoxic T Lymphocytes through Connexin-43 Channels

“…Importantly, these augmented levels of miR-192-5p in post-co-cultured CTLs were not observed when the hypoxic B16F10 expressed shCx43, suggesting that hypoxic B16F10 cells transferred miR-192-5p to CTLs via a Cx43-dependent mechanism ( Figure 5 B). The transfer of miRNAs among cells could be mediated by EV (mainly by exosomes) [ 18 ] that also contain functional Cx43 channels [ 44 ], and/or by cell-cell GJIC [ 18 ]. Our results also suggest that hypoxic B16F10 cells transfer miR-192-5p to CTLs via a cell-to-cell contact-dependent manner, given that the levels of this miRNA did not changed in CTLs after transwell co-cultures with B16F10 cells ( Figure 5 C).…”

“…Interestingly, the mobility of miRNAs between cells is not limited only to an exosome-mediated mechanism. Indeed, recent data suggests that miRNAs could be transferred between contacting cells via gap junctions (GJs), and it has been proposed as a novel pathway for intercellular regulation of gene expression [ 17 , 18 ]. GJs are connexin (Cx)-formed channels that through the cell-to-cell shuttling of small molecules regulate a plethora of physiological functions, including immunity [ 19 ].…”