ArticleThe EMBO journal2023
HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Challenges and limitations for live cell imaging in extreme cold.Methods and applications in fluorescence · 2026Article
- Roles of RNA-Binding Nuclear Proteins in Alzheimer's Disease Pathophysiology.ACS pharmacology & translational science · 2026Review
- Review
- HNRNPH1 drives glioblastoma progression by regulating the splicing of cell cycle genes.Cell death & disease · 2026Article
- Nonsense-mediated mRNA decay and associated splicing patterns in neurodevelopmental disorders.Frontiers in molecular biosciences · 2026Review
- Integrative RNA-seq and iRIP-seq analysis links SNRPA overexpression to transcriptomic and splicing alterations in hepatocellular carcinoma cells.Frontiers in oncology · 2026Article
- Ultra-Conserved Poison Exons Enable Rapid and Safe Splicing Factor Gene Expression Switches: A Hypothesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Molecular mediators of cold adaptation in mammalian cells.Communications biology · 2025Review
- Stabilizing a mammalian RNA thermometer confers neuroprotection in subarachnoid hemorrhage.Nature communications · 2025Article
- PTK6 drives HNRNPH1 phase separation to activate autophagy and suppress apoptosis in colorectal cancer.Autophagy · 2025Article
- hnRNPH1: A Multifaceted Regulator in RNA Processing and Disease Pathogenesis.International journal of molecular sciences · 2025Review
- Promoting health and survival through lowered body temperature.Nature aging · 2025Review
- CRISPR-based genetic screens in human pluripotent stem cells derived neurons and brain organoids.Cell and tissue research · 2025Review
- hnRNPH1 Inhibits Influenza Virus Replication by Binding Viral RNA.Microorganisms · 2024Article
- Thermoregulated transcriptomics: the molecular basis and biological significance of temperature-dependent alternative splicing.The Biochemical journal · 2024Review
- Trends and hotspots of the neuroprotection of hypothermia treatment: A bibliometric and visualized analysis of research from 1992 to 2023.CNS neuroscience & therapeutics · 2024Article
- Cold-shock proteome of myoblasts reveals role of RBM3 in promotion of mitochondrial metabolism and myoblast differentiation.Communications biology · 2024Article
- Mild hypothermia promotes neuronal differentiation of human neural stem cells via RBM3-SOX11 signaling pathway.iScience · 2024Article
- Rbm3 deficiency leads to transcriptome-wide splicing alterations.RNA biology · 2024Article
- HNRNPH1 regulates the neuroprotective cold-shock protein RBM3 expression through poison exon exclusion.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Enhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons. We found that RBM3 mRNA and protein levels are robustly regulated by several splicing factors, with heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) being the strongest positive regulator. Splicing analysis revealed that moderate hypothermia significantly represses the inclusion of a poison exon, which, when retained, targets the mRNA for nonsense-mediated decay. Importantly, we show that HNRNPH1 mediates this cold-dependent exon skipping via its thermosensitive interaction with a G-rich motif within the poison exon. Our study provides novel mechanistic insights into the regulation of RBM3 and provides further targets for neuroprotective therapeutic strategies.
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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 Socratic graph.