ArticleBrain : a journal of neurology2021
Aberrant cytoplasmic intron retention is a blueprint for RNA binding protein mislocalization in VCP-related amyotrophic lateral sclerosis.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- Article
- EIciRNAs in focus: current understanding and future perspectives.RNA biology · 2025Review
- An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.Science advances · 2025Article
- FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS.medRxiv : the preprint server for health sciences · 2025Article
- Decoding subcellular RNA localization one molecule at a time.Genome biology · 2025Review
- Review
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- Elucidating the pathobiology of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) with its expanded RNA structure formation and proteinopathy.Scientific reports · 2024Article
- Article
- TDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?International journal of molecular sciences · 2022Review
- Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS.Nature communications · 2022Article
- High-Altitude Stress Orchestrates mRNA Expression and Alternative Splicing of Ovarian Follicle Development Genes in Tibetan Sheep.Animals : an open access journal from MDPI · 2022Article
- Physiological intron retaining transcripts in the cytoplasm abound during human motor neurogenesis.Genome research · 2022Article
- HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS.Acta neuropathologica · 2022Article
- Phenotype of VCP Mutations in Chinese Amyotrophic Lateral Sclerosis Patients.Frontiers in neurology · 2022Article
- Review
- Reactive astrocytes in ALS display diminished intron retention.Nucleic acids research · 2021Article
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9 authors at 3 institutions in 4 countries.
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Abstract
We recently described aberrantly increased cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as new hallmarks of amyotrophic lateral sclerosis (ALS). However, the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep sequencing of nuclear and cytoplasmic fractions of human induced pluripotent stem cells undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. Specifically, we identify >100 IRTs with increased cytoplasmic abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins. Remarkably, TDP-43, SFPQ and FUS-RNA binding proteins known for nuclear-to-cytoplasmic mislocalization in ALS-abundantly and specifically bind to this aberrant cytoplasmic pool of IRTs. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.
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