Local mRNA translation in long-term maintenance of axon health and function

Kim, Eun Jin; Jung, Hosung

doi:10.1016/j.conb.2020.01.006

Cited by 28 publications

(26 citation statements)

References 68 publications

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“…Notably, we also observed sporadic enrichment of Arhgap11a mRNAs along the basal process (Figures 1I, 5F). While this could be a result of collective RNA trafficking to basal endfeet, such enrichment could also represent local translation "hotspots" in the basal process, as proposed in axons (Kim and Jung, 2020).…”

Section: Localized Rho-gtpase Signaling Controls Rgc Morphologymentioning

confidence: 97%

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Pilaz

Joshi

Liu

et al. 2020

Preprint

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mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5′UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development.

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Section: Localized Rho-gtpase Signaling Controls Rgc Morphologymentioning

confidence: 97%

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Pilaz

Joshi

Liu

et al. 2020

Preprint

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“…Gumy et al illustrated that the sets of genes are distinctively expressed in mouse embryonic and adult DRG axons by using compartmentalized neuronal culture systems [36] ( Figure 1A). An axon contains a collection of mRNA that is directly involved in multiple pathways of stimulation responsive regulation [27,[37][38][39]. Using microarray analysis of compartmentalized culture systems, 2,627 and 2,924 transcripts of the mouse embryonic and adult DRG axonal mRNA were identified, respectively, that were subjected to further analysis.…”

Section: Axonal Mrna and Protein Local Synthesismentioning

confidence: 99%

“…Identifying axonal mRNA leads us to study the injury-responsive axonal protein synthesis, revealing that protein local synthesis is essential for regulating axon regeneration [2,25,[27][28][29][30][31][32][33][34][35]39,[42][43][44].…”

Section: Axonal Mrna and Protein Local Synthesismentioning

confidence: 99%

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Comparative gene expression profiling reveals the mechanisms of axon regeneration

Lee

Cho

2020

The FEBS Journal

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Axons are vulnerable to injury, potentially leading to degeneration or neuronal death. While neurons in the central nervous system fail to regenerate, neurons in the peripheral nervous system are known to regenerate. Since it has been shown that injury-response signal transduction is mediated by gene expression changes, expression profiling is a useful tool to understand the molecular mechanisms of regeneration. Axon regeneration is regulated by injury-responsive genes induced in both neurons and their surrounding non-neuronal cells. Thus, an experimental setup for the comparative analysis between regenerative and non-regenerative conditions is essential to identify ideal targets for the promotion of regeneration-associated genes and to understand the mechanisms of axon regeneration. Here, we review the original research that shows the key factors regulating axon regeneration, in particular by using comparative gene expression profiling in diverse systems.

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“…Neurons are unique due to their extended axonal processes, and many important cellular processes take place in the axons including translation of mRNA (21)(22)(23). Of more than 20 genes examined in axons four showed prominent differential 3'UTR/CDS in or around axons ( Fig.…”

Section: Cellular Compartmentalization Of the I3'utrsmentioning

confidence: 99%

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

Yang

Gozali

et al. 2020

Preprint

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Mature mRNA molecules are typically considered to be comprised of a 5’UTR, a 3’UTR and a coding region (CDS), all attached until degradation. Unexpectedly, however, there have been multiple recent reports of widespread differential expression of mRNA 3’UTRs and their cognate coding regions, resulting in the expression of isolated 3’UTRs (i3’UTRs); these i3’UTRs can be highly expressed, often in reciprocal patterns to their cognate CDS. Similar to the role of other lncRNAs, isolated 3’UTRs are likely to play an important role in gene regulation but little is known about the contexts in which they are deployed. To begin to parse the functions of i3’UTRs, here we carry out in vitro, in vivo and in silico analyses of differential 3’UTR/CDS mRNA ratio usage across tissues, development and cell state changes both for a select list of developmentally important genes as well as through unbiased transcriptome-wide analyses. Across two developmental paradigms we find a distinct switch from high i3’UTR expression of stem cell related genes in proliferating cells compared to newly differentiated cells. Our unbiased transcriptome analysis across multiple gene sets shows that regardless of tissue, genes with high 3’UTR to CDS ratios belong predominantly to gene ontology categories related to cell-type specific functions while in contrast, the gene ontology categories of genes with low 3’UTR to CDS ratios are similar and relate to common cellular functions. In addition to these specific findings our data provide critical information from which detailed hypotheses for individual i3’UTRs can be tested-with a common theme that i3’UTRs appear poised to regulate cell-specific gene expression and state.Significance StatementThe widespread existence and expression of mRNA 3’ untranslated sequences in the absence of their cognate coding regions (called isolated 3’UTRs or i3’UTRs) opens up considerable avenues for gene regulation not previously envisioned. Each isolated 3’UTR may still bind and interact with micro RNAs, RNA binding proteins as well as other nucleic acid sequences, all in the absence or low levels of cognate protein production. Here we document the expression, localization and regulation of i3’UTRs both within particular biological systems as well as across the transcriptome. As this is an entirely new area of experimental investigation these early studies are seminal to this burgeoning field.

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Local mRNA translation in long-term maintenance of axon health and function

Cited by 28 publications

References 68 publications

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Comparative gene expression profiling reveals the mechanisms of axon regeneration

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

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