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Transcriptomics of Neurochondrin (NCDN)-depleted and control U251 glioblastoma cells

ABSTRACT: Pre mRNA splicing is orchestrated by the spliceosome; a dynamic and highly regulated ribonucleoprotein complex composed of five small nuclear ribonucleoprotein particles (snRNPs). Despite extensive studies, the biogenesis of snRNPs remains incompletely understood. Here, we identify neurochondrin (NCDN) as a critical regulator of pre-U5 snRNP biogenesis in the cytoplasm. NCDN directly binds to AAR2 and facilitates its release from the PRPF8−AAR2−EFTUD2 assembly intermediate, a key step required for U5 snRNP maturation. Loss of NCDN causes the accumulation of this intermediate, resulting in a decreased level of mature U5 snRNP. Spliceosome dysregulation often leads to alternative splicing abnormalities implicated in cancer. Indeed, NCDN deficiency suppresses tumor cell proliferation and induces apoptosis, while high NCDN expression promotes tumor cell growth and correlates with poor survival in glioblastoma patients. Transcriptome analysis reveals that loss of NCDN causes widespread alternative splicing defects and changes in gene expression. Aberrant splicing of tumor-associated genes may contribute to tumor progression in glioblastoma. Collectively, these results establish NCDN as an essential chaperone factor for U5 snRNP assembly and spliceosome function, and highlight NCDN as a potential therapeutic target in the treatment of glioma with elevated NCDN expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE299993 | GEO | 2026/07/11

REPOSITORIES: GEO

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