Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons

Turner-Bridger, Benita; Jakobs, Maximilian Ah; Mureşan, Leila; Wong, Hovy Ho-Wai; Franze, Kristian; Harris, William A.; Holt, Christine E.

doi:10.1073/pnas.1806189115

Cited by 78 publications

(107 citation statements)

References 94 publications

(138 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many components of pre‐miRNA dynamics that we report here resemble those of mRNA in axons. We document similar bidirectional trafficking (Leung et al , ; Turner‐Bridger et al , ) and faster anterograde than retrograde transport (Turner‐Bridger et al , ). Maximal velocities and average speed of active puncta are also comparable (Leung et al , ; Turner‐Bridger et al , ).…”

Section: Discussionsupporting

confidence: 82%

“…We document similar bidirectional trafficking (Leung et al , ; Turner‐Bridger et al , ) and faster anterograde than retrograde transport (Turner‐Bridger et al , ). Maximal velocities and average speed of active puncta are also comparable (Leung et al , ; Turner‐Bridger et al , ). In contrast to our study, the dominant mRNA trajectories previously measured (Turner‐Bridger et al , ) were confined and diffusive, with only a small proportion being directed, while the majority of puncta we detected adopted an overall active and directed trajectory.…”

Section: Discussionsupporting

confidence: 82%

“…Maximal velocities and average speed of active puncta are also comparable (Leung et al , ; Turner‐Bridger et al , ). In contrast to our study, the dominant mRNA trajectories previously measured (Turner‐Bridger et al , ) were confined and diffusive, with only a small proportion being directed, while the majority of puncta we detected adopted an overall active and directed trajectory. This disparity in motion type frequencies may be due to technical disparities, or reflect actual biological differences.…”

Section: Discussionmentioning

confidence: 82%

“…It is technically very challenging to study transport of endogenous miRNAs due to their short length, making classic tools such as the long MS2 tagging ineffective. To investigate mechanisms of miRNA dynamics, we have adapted MB, a technique already employed by others to track miRNA localization, although not their transport dynamics [e.g., (Földes‐Papp et al , )], and mRNA trafficking in living cells including in Xenopus RGC axons (Turner‐Bridger et al , ). The series of data we provide here collectively suggest that the MB we designed specifically detects pre‐miRNAs in axons.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have provided great insight into axonal mRNA trafficking (Alami et al , ; Leung et al , ; Turner‐Bridger et al , ). Many components of pre‐miRNA dynamics that we report here resemble those of mRNA in axons.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits

et al. 2020

View full text Add to dashboard Cite

Various species of non‐coding RNAs (ncRNAs) are enriched in specific subcellular compartments, but the mechanisms orchestrating their localization and their local functions remain largely unknown. We investigated both aspects using the elongating retinal ganglion cell axon and its tip, the growth cone, as models. We reveal that specific endogenous precursor microRNAs (pre‐miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (Sema3A), pre‐miRNAs are processed specifically within axons into newly generated miRNAs, one of which, in turn, silences the basal translation of tubulin beta 3 class III (TUBB3), but not amyloid beta precursor protein (APP). At the organismal level, these mature miRNAs are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of ncRNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated miRNAs are critical components of a ncRNA‐based signaling pathway that transduces environmental signals into the structural remodeling of subcellular compartments.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits

et al. 2020

View full text Add to dashboard Cite

show abstract

Brain‐derived neurotrophic factor‐induced regulation of RNA metabolism in neuronal development and synaptic plasticity

et al. 2022

View full text Add to dashboard Cite

The neurotrophin brain‐derived neurotrophic factor (BDNF) plays multiple roles in the nervous system, including in neuronal development, in long‐term synaptic potentiation in different brain regions, and in neuronal survival. Alterations in these regulatory mechanisms account for several diseases of the nervous system. The synaptic effects of BDNF mediated by activation of tropomyosin receptor kinase B (TrkB) receptors are partly mediated by stimulation of local protein synthesis which is now considered a ubiquitous feature in both presynaptic and postsynaptic compartments of the neuron. The capacity to locally synthesize proteins is of great relevance at several neuronal developmental stages, including during neurite development, synapse formation, and stabilization. The available evidence shows that the effects of BDNF–TrkB signaling on local protein synthesis regulate the structure and function of the developing and mature synapses. While a large number of studies have illustrated a wide range of effects of BDNF on the postsynaptic proteome, a growing number of studies also point to presynaptic effects of the neurotrophin in the local regulation of the protein composition at the presynaptic level. Here, we will review the latest evidence on the role of BDNF in local protein synthesis, comparing the effects on the presynaptic and postsynaptic compartments. Additionally, we overview the relevance of BDNF‐associated local protein synthesis in neuronal development and synaptic plasticity, at the presynaptic and postsynaptic compartments, and their relevance in terms of disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications RNA Export and Localization > RNA Localization

show abstract

Hitting the mark: Localization of mRNA and biomolecular condensates in health and disease

Otis

Mowry

2023

WIREs RNA

View full text Add to dashboard Cite

Subcellular mRNA localization is critical to a multitude of biological processes such as development of cellular polarity, embryogenesis, tissue differentiation, protein complex formation, cell migration, and rapid responses to environmental stimuli and synaptic depolarization. Our understanding of the mechanisms of mRNA localization must now be revised to include formation and trafficking of biomolecular condensates, as several biomolecular condensates that transport and localize mRNA have recently been discovered. Disruptions in mRNA localization can have catastrophic effects on developmental processes and biomolecular condensate biology and have been shown to contribute to diverse diseases. A fundamental understanding of mRNA localization is essential to understanding how aberrations in this biology contribute the etiology of numerous cancers though support of cancer cell migration and biomolecular condensate dysregulation, as well as many neurodegenerative diseases, through misregulation of mRNA localization and biomolecular condensate biology.This article is categorized under: RNA Export and Localization > RNA Localization RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development

show abstract

Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons

Cited by 78 publications

References 94 publications

Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits

Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits

Brain‐derived neurotrophic factor‐induced regulation of RNA metabolism in neuronal development and synaptic plasticity

Hitting the mark: Localization of mRNA and biomolecular condensates in health and disease

Contact Info

Product

Resources

About