Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations

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Detalles Bibliográficos
Publicado en:	Nature Communications vol. 16, no. 1 (2025), p. 10460-10475
Autor principal:	Zhou, Sihang
Otros Autores:	Lizarazo, Simon, Chorghade, Sandip, Mouli, Leela, Cheng, Ruiying, K C, Rajendra, Kalsotra, Auinash, Van Bortle, Kevin
Publicado:	Nature Publishing Group
Materias:	Cancer Ribonucleoproteins (U2 small nuclear) Ontology Experiments Ribonucleoproteins (small nuclear) Ribonucleic acid > RNA Phenotypes Cell proliferation Alternative splicing RNA-protein interactions Hybridization Tumorigenesis Splicing factors Non-coding RNA Localization Genes Cell growth Defects DNA-directed RNA polymerase Subpopulations Environmental
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Descripción
Resumen:	Expansion of RNA polymerase III (Pol III) activity in cancer can activate the transcription of typically silent small RNA genes, including snaR-A (small NF90-associated RNA isoform A), a hominid-specific noncoding RNA that promotes cell proliferation through unclear mechanisms. Here, we show that snaR-A interacts with mRNA splicing factors, including the U2 small nuclear ribonucleoprotein (snRNP) subunit SF3B2, and localizes near subnuclear foci enriched in splicing machinery. Overexpression of snaR-A increases intron retention, a hallmark of inefficient splicing, whereas its depletion enhances splicing of mRNAs characterized by high U2 snRNP occupancy and nuclear speckle proximity. These improvements in splicing coincide with reduced cell proliferation, consistent with tumor-level patterns linking snaR-A to growth in primary cancers. Together, these findings identify snaR-A as a molecular antagonist of splicing and potential disease driver in cancer. We propose that snaR-A-related splicing perturbation may phenocopy splicing defects attributed to U2 snRNP mutations in cancer, eliciting an alternative, non-mutational mechanism of splicing dysregulation during tumorigenesis.Small RNAs such as snaR-A (small NF90-associated RNA isoform A) may contribute to cancer-related phenotypes. Here the authors find that snaR-A interacts with mRNA splicing factors in subnuclear foci and causes splicing defects in mRNA subpopulations, which is associated with increased cell proliferation, and poor outcomes in cancer patients.
ISSN:	2041-1723
DOI:	10.1038/s41467-025-65448-x
Fuente:	Health & Medical Collection