Zhou S et al., Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations. Nature Communications - snaR-A noncoding RNA interacts with U2 snRNP subunit SF3B2 and nuclear speckles, increasing intron retention and promoting proliferation in human cancer-relevant cells.

Study Highlights:
Using human cell lines (HEK293T, A549, THP-1) and tumor chromatin data, the authors combined biotinylated RNA pulldown mass spectrometry, PAR-CLIP/CLIP-qPCR, HCR-RNA-FISH, TSA-seq, and ultra-deep RNA-seq (IRFinder, rMATS) to map snaR-A interactions and splicing outcomes. snaR-A directly binds splicing factors and shows nucleotide-level crosslinking to the U2 snRNP protein SF3B2, and localizes to subnuclear foci adjacent to nuclear speckles and U6-containing sites. Functionally, snaR-A overexpression increases intron retention and selectively depletes SF3B2 protein, whereas snaR-A depletion reduces intron retention for transcripts with high U2 occupancy and speckle proximity. These splicing changes alter protein abundance for multiple targets and coincide with reduced proliferation after snaR-A depletion, consistent with tumor-level associations to growth.

Conclusion:
snaR-A acts as a molecular antagonist of U2-dependent splicing by interacting with SF3B2 and perturbing processing of specific mRNA subpopulations, promoting intron retention and proliferation in cancer-relevant contexts.

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Reference:
Zhou S., Lizarazo S., Chorghade S., Mouli L., Cheng R., Rajendra K. C., Kalsotra A., Van Bortle K. Cancer-associated snaR-A noncoding RNA interacts with core splicing machinery and disrupts processing of mRNA subpopulations. Nature Communications. 2025;16:10460. https://doi.org/10.1038/s41467-025-65448-x

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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