ArticlePloS one2013
KSRP modulation of GAP-43 mRNA stability restricts axonal outgrowth in embryonic hippocampal neurons.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- KHSRP-mediated decay of axonally localized prenyl-Cdc42 mRNA slows nerve regeneration.PLoS genetics · 2025Article
- Decoding protein-RNA interactions using CLIP-based methodologies.Nature reviews. Genetics · 2024Review
- Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms.Science (New York, N.Y.) · 2024Article
- Adipose-Derived Stem Cells Spontaneously Express Neural Markers When Grown in a PEG-Based 3D Matrix.International journal of molecular sciences · 2023Article
- KHSRP loss increases neuronal growth and synaptic transmission and alters memory consolidation through RNA stabilization.Communications biology · 2022Article
- Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs.Nucleic acids research · 2022Article
- Expression of Slit and Robo during remodeling of corticospinal tract in cervical spinal cord in middle cerebral artery occlusion rats.Molecular biology reports · 2021Article
- Axonal mRNA localization and translation: local events with broad roles.Cellular and molecular life sciences : CMLS · 2021Review
- Regulation of Fetal Genes by Transitions among RNA-Binding Proteins during Liver Development.International journal of molecular sciences · 2020Article
- Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell-based in vitro disease modeling: convergence of schizophrenia- and autism-related cellular phenotypes.Stem cell research & therapy · 2020Article
- Emerging Roles for 3' UTRs in Neurons.International journal of molecular sciences · 2020Review
- GAP-43 and BASP1 in Axon Regeneration: Implications for the Treatment of Neurodegenerative Diseases.Frontiers in cell and developmental biology · 2020Review
- Differential regulation of brain-derived neurotrophic factor (BDNF) expression in sensory neuron axons by miRNA-206.FEBS open bio · 2019Article
- Axonal mRNA transport and translation at a glance.Journal of cell science · 2018Review
- Expanding Axonal Transcriptome Brings New Functions for Axonally Synthesized Proteins in Health and Disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2018Review
- Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.Biochimica et biophysica acta. Molecular basis of disease · 2018Article
- CBX2 Inhibits Neurite Development by Regulating Neuron-Specific Genes Expression.Frontiers in molecular neuroscience · 2018Article
- KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression.Nature communications · 2017Article
- Axonal localization of neuritin/CPG15 mRNA is limited by competition for HuD binding.Journal of cell science · 2017Article
- K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The KH-type splicing regulatory protein (KSRP) promotes the decay of AU-rich element (ARE)-containing mRNAs. Although KSRP is expressed in the nervous system, very little is known about its role in neurons. In this study, we examined whether KSRP regulates the stability of the ARE-containing GAP-43 mRNA. We found that KSRP destabilizes this mRNA by binding to its ARE, a process that requires the presence of its fourth KH domain (KH4). Furthermore, KSRP competed with the stabilizing factor HuD for binding to these sequences. We also examined the functional consequences of KSRP overexpression and knockdown on the differentiation of primary hippocampal neurons in culture. Overexpression of full length KSRP or KSRP without its nuclear localization signal hindered axonal outgrowth in these cultures, while overexpression of a mutant protein without the KH4 domain that has less affinity for binding to GAP-43's ARE had no effect. In contrast, depletion of KSRP led to a rise in GAP-43 mRNA levels and a dramatic increase in axonal length, both in KSRP shRNA transfected cells and neurons cultured from Ksrp(+/-) and Ksrp(-/-) embryos. Finally we found that overexpression of GAP-43 rescued the axonal outgrowth deficits seen with KSRP overexpression, but only when cells were transfected with GAP-43 constructs containing 3' UTR sequences targeting the transport of this mRNA to axons. Together, our results suggest that KSRP is an important regulator of mRNA stability and axonal length that works in direct opposition to HuD to regulate the levels of GAP-43 and other ARE-containing neuronal mRNAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.