Identification of precursor micro<scp>RNA</scp>s within distal axons of sensory neuron

Kim, Hak Hee; Kim, Paul; Phay, Monichan; Yoo, Soonmoon

doi:10.1111/jnc.13140

Cited by 37 publications

(39 citation statements)

References 49 publications

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“…Similar to zebrafish, miR-31 expression is ubiquitous in the sea urchin embryo; however, it localizes to punctate structures that do not appear to be nuclear, a pattern that was found typical for only a few miRNAs, such as miR34b, in zebrafish embryos, and for a number of dendritic or axonic miRNAs, such as miR-26a, miR-124a, pre-miR-25 and pre-miR-433, in rats (Kye et al, 2007;Wang et al, 2013;Goldie et al, 2014;Kim et al, 2015). miRNAs or pre-miRNAs that show punctate localization in dendrites or axons are thought to be compartmentalized to perform localized activity-dependent translation (Goldie et al, 2014;Kim et al, 2015). Further study is required to identify the nature of the punctate pattern of miR-31 in the sea urchin embryo.…”

Section: Discussionmentioning

confidence: 99%

microRNA-31 modulates skeletal patterning in the sea urchin embryos

Stepicheva

Song

2015

Development

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MicroRNAs (miRNAs) are small non-coding RNAs that repress the translation and reduce the stability of target mRNAs in animal cells. microRNA-31 (miR-31) is known to play a role in cancer, bone formation and lymphatic development. However, studies to understand the function of miR-31 in embryogenesis have been limited. We examined the regulatory role of miR-31 in early development using the sea urchin as a model. miR-31 is expressed at all stages of development and its knockdown (KD) disrupts the patterning and function of primary mesenchyme cells (PMCs), which form the embryonic skeleton spicules. We identified that miR-31 directly represses Pmar1, Alx1, Snail and VegfR7 within the PMC gene regulatory network using reporter constructs. Further, blocking the miR-31-mediated repression of Alx1 and/or VegfR7 in the developing embryo resulted in defects in PMC patterning and skeletogenesis. The majority of the mislocalized PMCs in miR-31 KD embryos did not express VegfR10, indicating that miR-31 regulates VegfR gene expression within PMCs. In addition, miR-31 indirectly suppresses Vegf3 expression in the ectoderm. These results indicate that miR-31 coordinately suppresses genes within the PMCs and in the ectoderm to impact PMC patterning and skeletogenesis. This study identifies the novel function and molecular mechanism of miR-31-mediated regulation in the developing embryo.

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Section: Discussionmentioning

confidence: 99%

microRNA-31 modulates skeletal patterning in the sea urchin embryos

Stepicheva

Song

2015

Development

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“…However, several lines of evidence indicate that axons can sprout after injury in adult central nervous system [8–12]. Recent studies show that distal axons of embryonic cortical neurons contain miRNA machinery proteins, Dicer and argonaut 2 protein (Ago2) and are enriched with miRNAs that can locally regulate axonal growth [13–15]. For example, alteration of the miR-17-92 cluster and miR-29c levels in the cultured neurons promote axonal growth by suppressing their target genes that inhibit axonal growth even under the inhibitory environment with chondroitin sulfate proteoglycans [16,17].…”

Section: Introductionmentioning

confidence: 99%

Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons

et al. 2016

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Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.

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“…miRNAs localized to the axons play a critical role in axonal function and viability [8]. In addition to the mature miRNAs, it has also been reported that precursor miRNAs (pre-miRNAs) are localized to axons and dendrites [15–17]. Consistent with pre-miRNAs being present in axons, components of the RISC complex involved in miRNA processing have also been shown to be present in the axon [18–19].…”

Section: Introductionmentioning

confidence: 99%

Axonal localization and mitochondrial association of precursor microRNA 338

Vargas

Kar

Kowalak

et al. 2016

Cell. Mol. Life Sci.

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microRNAs (miRNAs) selectively localize to subcompartments of the neuron, such as dendrites, axons and presynaptic terminals, where they regulate the local protein synthesis of their putative target genes. In addition to mature miRNAs, precursor miRNAs (pre-miRNAs) have also been shown to localize to somatodendritic and axonal compartments. miRNA-338 (miR-338) regulates the local expression of several nuclear-encoded mitochondrial mRNAs within axons of sympathetic neurons. Previous work has shown that precursor miR-338 (pre-miR-338) introduced into the axon can be locally processed into mature miR-338, where it can regulate local ATP synthesis. However, the mechanisms underlying the localization of pre-miRNAs to the axonal compartment remain unknown. In this study, we investigated the axonal localization of pre-miR-338. Using proteomic and biochemical approaches, we provide evidence for the localization of pre-miR-338 to distal neuronal compartments and identify several constituents of the pre-miR-338 ribonucleoprotein complex. Furthermore, we found that pre-miR-338 is associated with the mitochondria in axons of superior cervical ganglion (SCG) neurons. The maintenance of mitochondrial function within axons requires the precise spatio-temporal synthesis of nuclear-encoded mRNAs, some of which are regulated by miR-338. Therefore, the association of pre-miR-338 with axonal mitochondria could serve as a reservoir of mature, biologically active miRNAs, which could coordinate the intra-axonal expression of multiple nuclear-encoded mitochondrial mRNAs.

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Identification of precursor microRNAs within distal axons of sensory neuron

Cited by 37 publications

References 49 publications

microRNA-31 modulates skeletal patterning in the sea urchin embryos

microRNA-31 modulates skeletal patterning in the sea urchin embryos

Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons

Axonal localization and mitochondrial association of precursor microRNA 338

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