ArticleProceedings of the National Academy of Sciences of the United States of America2010
Quaking I controls a unique cytoplasmic pathway that regulates alternative splicing of myelin-associated glycoprotein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
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- SRSF10 regulates oligodendrocyte differentiation during mouse central nervous system development by modulating pre-mRNA splicing.Nucleic acids research · 2025Article
- The Roles of hnRNP Family in the Brain and Brain-Related Disorders.Molecular neurobiology · 2024Review
- The RNA-binding protein quaking is upregulated in nitrofen-induced congenital diaphragmatic hernia lungs at the end of gestation.Pediatric surgery international · 2024Article
- Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus.Frontiers in molecular neuroscience · 2024Article
- Mutant KRAS Mediates circARFGEF2 Biogenesis to Promote Lymphatic Metastasis of Pancreatic Ductal Adenocarcinoma.Cancer research · 2023Article
- RNA-binding proteins regulating the CD44 alternative splicing.Frontiers in molecular biosciences · 2023Review
- Proteomic signatures of schizophrenia-sourced iPSC-derived neural cells and brain organoids are similar to patients' postmortem brains.Cell & bioscience · 2022Article
- Irrespective of Plaque Activity, Multiple Sclerosis Brain Periplaques Exhibit Alterations of Myelin Genes and a TGF-Beta Signature.International journal of molecular sciences · 2022Article
- The Quaking RNA-binding proteins as regulators of cell differentiation.Wiley interdisciplinary reviews. RNA · 2022Review
- Definition of germ layer cell lineage alternative splicing programs reveals a critical role for Quaking in specifying cardiac cell fate.Nucleic acids research · 2022Article
- Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation.Genome biology · 2022Article
- hnRNP A1 in RNA metabolism regulation and as a potential therapeutic target.Frontiers in pharmacology · 2022Review
- Article
- LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells.Cell death & disease · 2021Article
- Oligodendrocyte lineage cells and depression.Molecular psychiatry · 2021Review
- RNA packaging into extracellular vesicles: An orchestra of RNA-binding proteins?Journal of extracellular vesicles · 2020Review
- mNeuron · 2020Article
- Soluble Siglec-14 glycan-recognition protein is generated by alternative splicing and suppresses myeloid inflammatory responses.The Journal of biological chemistry · 2018Article
- Oligodendrocyte differentiation of induced pluripotent stem cells derived from subjects with schizophrenias implicate abnormalities in development.Translational psychiatry · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Precise control of alternative splicing governs oligodendrocyte (OL) differentiation and myelination in the central nervous system (CNS). A well-known example is the developmentally regulated expression of splice variants encoding myelin-associated glycoprotein (MAG), which generates two protein isoforms that associate with distinct cellular components crucial for axon-glial recognition during myelinogenesis and axon-myelin stability. In the quakingviable (qk(v)) hypomyelination mutant mouse, diminished expression of isoforms of the selective RNA-binding protein quaking I (QKI) leads to severe dysregulation of MAG splicing. The nuclear isoform QKI-5 was previously shown to bind an intronic element of MAG and modulate alternative exon inclusion from a MAG minigene reporter. Thus, QKI-5 deficiency was thought to underlie the defects of MAG splicing in the qk(v) mutant. Surprisingly, we found that transgenic expression of the cytoplasmic isoform QKI-6 in the qk(v) OLs completely rescues the dysregulation of MAG splicing without increasing expression or nuclear abundance of QKI-5. In addition, cytoplasmic QKI-6 selectively associates with the mRNA that encodes heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), a well-characterized splicing factor. Furthermore, QKI deficiency in the qk(v) mutant results in abnormally enhanced hnRNPA1 translation and overproduction of the hnRNPA1 protein but not hnRNPA1 mRNA, which can be successfully rescued by the QKI-6 transgene. Finally, we show that hnRNPA1 binds MAG pre-mRNA and modulates alternative inclusion of MAG exons. Together, these results reveal a unique cytoplasmic pathway in which QKI-6 controls translation of the splicing factor hnRNPA1 to govern alternative splicing in CNS myelination.
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