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bioRxiv · 10.64898/2026.11.09.765366

Transcript-resolved analysis identifies lncRNA carrier architectures and selective nucleolar enrichment in colorectal cancer

Flowers, B.·Lialios, P.·Park, E.·Denniss, C.·Burgess, R. J.·Lee, J.-S.
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Abstract

Long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) are commonly characterized at the gene level, obscuring processed RNA architectures and regional localization. In renal cell carcinoma, a processed CRNDE isoform retaining an ultraconserved element (UCE) with a C/D snoRNA-like region promotes pre-60S maturation. Here, we examined CRNDE UCE-region representation and integrated CRC tumor expression and clinical evidence with published HEK293 cross-linking and immunoprecipitation (CLIP) profiles for C/D small nucleolar ribonucleoprotein (snoRNP) proteins and long-read sequencing to identify retained CLIP-supported regions. CRNDE was upregulated in 49 of 50 paired tumors, and UCE-region signal was detected in 380 of 382 assessable primary tumors, although total CRNDE abundance showed little association with stage or outcome. Processed UCE-retaining CRNDE transcripts were identified in Caco-2 cells. Integration identified 1,714 disease-supported lncRNAs with CLIP overlap; among 576 non-CRNDE candidates, 188 CLIP-supported regions were retained within processed transcripts from 65 loci in both CRC cell models. Region-directed RT-qPCR following pre-ribosome sequential extraction revealed preferential enrichment of selected JPX, DLEU2, and LINC00630 RNA populations in the core nucleolar fraction relative to broader transcript-region measurements in both cell lines. These findings identify retained-region transcript architectures and reveal region-dependent nucleolar enrichment not apparent from broader transcript measurements.

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Flowers, B., Lialios, P., Park, E., Denniss, C., Burgess, R. J., Lee, J.-S.. 2026-11-12. Transcript-resolved analysis identifies lncRNA carrier architectures and selective nucleolar enrichment in colorectal cancer. https://doi.org/10.64898/2026.11.09.765366

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