Ask about this productRelated genes to: Clns1a antibody
- Gene:
- CLNS1A NIH gene
- Name:
- chloride nucleotide-sensitive channel 1A
- Previous symbol:
- CLCI
- Synonyms:
- ICln
- Chromosome:
- 11q14.1
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-16
- Date modifiied:
- 2016-02-05
Related products to: Clns1a antibody
Related articles to: Clns1a antibody
- The assembly of uridine-rich small nuclear ribonucleoproteins (U snRNPs), the central catalytic components of the spliceosome, is a highly organised, multi-step process orchestrated by several multi-protein complexes. Structural analyses have provided valuable insights into their overall architecture. However, critical information on the regulation of U snRNP assembly is still lacking. In this study, we used AlphaFold 3 to model the human 6S intermediate complex consisting of full-length pICln and five Sm proteins SmD1/D2/E/F/G. The available crystal structure used truncated non-vertebrate proteins, omitting the highly flexible C-terminal segments to permit crystallisation. However, the C-terminus of pICln has since been recognised as regulatory region, making full-length computational models an appropriate way to elucidate its structural and functional roles. By integrating modelling with biochemical data from previous studies, our results support a model in which the phosphorylation-dependent regulation of the pICln-SmG interface facilitates downstream assembly steps in vertebrates, including the regulated displacement of pICln by the SmD3/B dimer. According to this model, ULK1-dependent serine phosphorylation in the C-terminal α-helix of pICln may abrogate the secondary structure and weakens its interaction with SmG, favouring ring opening. This complementary approach elucidates the roles of regulatory regions in pICln that were previously inaccessible to crystallographic analysis and provides a framework for targeted experimental validation. - Source: PubMed
Publication date: 2025/12/16
Grimmler MatthiasReinhart MarcoAlers SebastianPeter Christoph - The blood-brain barrier (BBB) plays a central role in maintaining the ionic milieu required for neuronal activity and in translating neuronal activity in a local elevation in cerebral blood flow (CBF). However, the molecular repertoire of the human BBB remains poorly defined. Here, we performed a systematic transcriptomic analysis of 672 genes using eight independent RNA-Seq datasets generated from the human brain endothelial cell line hCMEC/D3, the most widely used model of the human BBB. We focused on ion channels, ion transporters, G protein-coupled receptors (GPCRs), and Receptor Tyrosine Kinases (RTKs), which govern ionic homeostasis, barrier integrity, and CBF. Among the most abundantly expressed ion transporters were subunits of the mitochondrial F-type ATPase complex (F-type ATPase α subunit, F-type ATPase β subunit, F-type ATPase C subunit), reflecting the high metabolic demands of the BBB. Key regulators of intracellular Ca homeostasis, including SERCA2, PMCA1/4, and SPCA1, were consistently detected, supporting efficient Ca clearance across endoplasmic reticulum (ER), plasma membrane, and Golgi compartments. Our analysis of ion channels revealed a selective repertoire with prominent expression of Cl-permeable channels (CLIC1/4, CLNS1A, VDAC1-3, VRAC) and various K-permeable channels, including IK/K3.1, K2.1, K1.2, BK, K4.1, and TREK-1. Na-permeable channels (ENaC and NALCN), non-selective cation channels (TRP, HCN2/3), and ER- (InsPRs, TRICs, and putative leak channels), and lysosomes-associated (TRPML1 and TPCs) channels were also detected. Additionally, we identified transcripts for mechanosensitive channels (PIEZO1, TACAN, TMC7, TMEM63B) and gap junction proteins (Cx43, Cx45, Cx47), as well as a broad array of ionotropic and metabotropic receptors, including purinergic, adenosine, histamine, GABA, adrenergic and nicotinic receptors. Growth factor-related RTKs (FGFR, IGFR, EGFR, PDGFR, VEGFR) were consistently expressed, underscoring their role in angiogenesis, endothelial-pericyte interactions, and BBB integrity. This meta-analysis highlights the conserved expression of transporter genes across datasets, contrasted with lower and more variable expression of ion channels and receptors, suggesting that the latter may be context-dependent and dynamically regulated. These findings provide a reference framework for understanding the human BBB transportome, offering new insights into the molecular toolkit of the human BBB to support future investigations into the role of endothelial ion transport in neurological disorders. - Source: PubMed
Publication date: 2025/12/18
Scarpellino GiorgiaBrunetti ValentinaScolari FrancescaVisentin LucaBiella Gerardo RosarioRuffinatti Federico AlessandroMoccia Francesco - Protein arginine methyltransferase 5 (PRMT5) catalyzes symmetric arginine dimethylation (Rme2s) of RNA-binding proteins and influences RNA splicing and gene expression. However, how PRMT5 couples splicing to productive transcript output remains unclear. We show that a major function of PRMT5 is to promote chromatin escape of mRNAs, designated as genomically retained incompletely processed polyadenylated transcripts (GRIPPs). Using nascent and spike-in normalized fractionated transcriptomics with proteomics, we find that PRMT5 inhibition in mammalian cells causes polyadenylated mRNA and Smith antigen (Sm) protein accumulation on chromatin. These retained transcripts are intron rich and splice slowly. PRMT5 inhibition and isogenic SNRPB mutants demonstrate that Sm tail methylation is essential to prevent RNA detention on chromatin. Biochemical assays reveal that the SMN Tudor domain competes with nucleic acid binding of methylated Sm tails. We conclude that PRMT5 ensures mRNA processing and nuclear export by preventing aberrant chromatin retention, highlighting arginine methylation as a key regulator of RNA-chromatin dynamics. - Source: PubMed
Publication date: 2025/10/13
DeAngelo Joseph DMaron Maxim IRoth Jacob SHegde SubraySilverstein Aliza MGupta VarunStransky StephanieBasken JoelAzofeifa JoeyQuery Charles CSidoli SimoneGamble Matthew JShechter David - Protein arginine methyltransferase 5 (PRMT5) is a promising cancer target, yet it is unclear which PRMT5 roles underlie this vulnerability. Here, we establish that PRMT5 inhibition induces a special class of unspliced introns, called detained introns (DIs). We used the depletion of CLNS1A, a PRMT5 cofactor that specifically enables Sm protein methylation, to interrogate the impact of DIs. We found that the disruption of Sm protein methylation is sufficient to induce DI upregulation, cell cycle defects, and loss of viability. Finally, we discovered that PRMT5-regulated DIs, and the impacted genes, are highly conserved across human, and also mouse, cell lines but display little interspecies conservation. Despite this, human and mouse DIs have convergent impacts on proliferation by affecting essential components of proliferation-regulating complexes. Together, these data argue that the PRMT5-splicing axis, and particularly appropriate DI splicing, underlie cancer's vulnerability to PRMT5 inhibitors. - Source: PubMed
Publication date: 2025/06/20
Fowler Colin EO'Hearn Natalie ASalus Griffin JSingh ArundeepBoutz Paul LLees Jacqueline A - Pathogenic CD4 T cells drive autoimmunity in diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Through a forward genetic screen, we identified chloride nucleotide-sensitive channel 1A (CLNS1A) as a key regulator of inflammation in the experimental autoimmune encephalomyelitis (EAE) model of MS. CLNS1A is expressed in several subsets of CD4 T cells, including pathogenic T helper 17 (pT17) cells. Deletion of in T cells resulted in DNA damage, cell cycle arrest, impaired T cell proliferation, and effector function, thereby protecting mice from both EAE and IBD. We found that CLNS1A interacts with protein arginine methyl transferase 5 (PRMT5). Moreover, CLNS1A regulates symmetric histone dimethylation and the expression of genes involved in DNA repair, replication, and cell cycle progression. Thus, CLNS1A plays an important role in CD4 T cells by promoting genome stability and cell cycle progression. - Source: PubMed
Publication date: 2025/06/20
Wang LiweiNoyer LucileJishage MikiWang Yin-HuTao Anthony YMcDermott MaxwellGando IvanSidhu IkjotHu KeZhong LiSun KatherineDrmic DominikKaufmann UlrikeFeske Stefan