ArticleDevelopmental neurobiology2014
Dysregulation of the axonal trafficking of nuclear-encoded mitochondrial mRNA alters neuronal mitochondrial activity and mouse behavior.
Article in Developmental neurobiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Neurotoxicologically Outcomes of Perinatal Chlordiazepoxide Exposure on the Fetal Prefrontal Cortex Cells in Rat Pup : Chlordiazepoxide Effects on Fetal Prefrontal Cortex.Galen medical journal · 2025Article
- Metabolic Regulation of Mitochondrial Protein Biogenesis from a Neuronal Perspective.Biomolecules · 2022Review
- Review
- Co-transport of the nuclear-encoded Cox7c mRNA with mitochondria along axons occurs through a coding-region-dependent mechanism.Journal of cell science · 2022Article
- Brain Mitochondrial Dysfunction: A Possible Mechanism Links Early Life Anxiety to Alzheimer's Disease in Later Life.Aging and disease · 2022Article
- Axonal mRNA localization and translation: local events with broad roles.Cellular and molecular life sciences : CMLS · 2021Review
- Mitochondrial support and local translation of mitochondrial proteins in synaptic plasticity and function.Histology and histopathology · 2021Review
- The functional organization of axonal mRNA transport and translation.Nature reviews. Neuroscience · 2021Review
- Neurodegeneration and axonal mRNA transportation.American journal of neurodegenerative disease · 2021Review
- Molecular mechanisms behind mRNA localization in axons.Open biology · 2020Review
- Deregulated Local Protein Synthesis in the Brain Synaptosomes of a Mouse Model for Alzheimer's Disease.Molecular neurobiology · 2020Article
- Axon TRAP reveals learning-associated alterations in cortical axonal mRNAs in the lateral amgydala.eLife · 2019Article
- Evidence for Compartmentalized Axonal Mitochondrial Biogenesis: Mitochondrial DNA Replication Increases in Distal Axons As an Early Response to Parkinson's Disease-Relevant Stress.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- mRNP assembly, axonal transport, and local translation in neurodegenerative diseases.Brain research · 2018Review
- Axonal mRNA transport and translation at a glance.Journal of cell science · 2018Review
- To the end of the line: Axonal mRNA transport and local translation in health and neurodegenerative disease.Developmental neurobiology · 2018Review
- Molecular determinants of cytochrome C oxidase IV mRNA axonal trafficking.Molecular and cellular neurosciences · 2017Article
- Axonal localization and mitochondrial association of precursor microRNA 338.Cellular and molecular life sciences : CMLS · 2016Article
- A heterogeneous population of nuclear-encoded mitochondrial mRNAs is present in the axons of primary sympathetic neurons.Mitochondrion · 2016Article
- Dysregulated axonal RNA translation in amyotrophic lateral sclerosis.Wiley interdisciplinary reviews. RNA · 2016Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Local translation of nuclear-encoded mitochondrial mRNAs is essential for mitochondrial activity, yet there is little insight into the role that axonal trafficking of these transcripts play in neuronal function and behavior. Previously, we identified a 38 nucleotide stem-loop structure (zipcode) in the 3' untranslated region of the Cytochrome C oxidase IV (COXIV) mRNA that directs the transport of a reporter mRNA to the axon of superior cervical ganglion neurons (SCG). Overexpression of a chimeric reporter mRNA with the COXIV zipcode competed with the axonal trafficking of endogenous COXIV mRNA, and led to attenuated axon growth in SCG neurons. Here, we show that exogenous expression of the COXIV zipcode in cultured SCG neurons also results in the reduction of local ATP levels and increases levels of reactive oxygen species (ROS) in the axon. We took advantage of this "competition" phenotype to investigate the in vivo significance of axonal transport of COXIV mRNA. Toward this end, we generated transgenic mice expressing a fluorescent reporter fused to COXIV zipcode under a forebrain-specific promoter. Immunohistological analyses and RT-PCR analyses of RNA from the transgenic mouse brain showed expression of the reporter in the deep layer neurons in the pre-frontal and frontal cortex. Consistent with the in vitro studies, we observed increased ROS levels in neurons of these transgenic animals. A battery of behavioral tests on transgenic mice expressing the COXIV zipcode revealed an "anxiety-like" behavioral phenotype, suggesting an important role for axonal trafficking of nuclear-encoded mitochondrial mRNAs in neuronal physiology and animal behavior.
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