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

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.