Abstract
BACKGROUND: Ultraconserved regions (UCRs) encompass 481 DNA segments exceeding 200 base pairs (bp), displaying 100% sequence identity across humans, mice, and rats, indicating profound conservation across taxa and pivotal functional roles in human health and disease. Despite two decades since their discovery, many UCRs remain to be explored owing to incomplete annotation, particularly of newly identified long non-coding RNAs (lncRNAs), and limited data aggregation in large-scale databases. This study offers a comprehensive functional map of 481 UCRs, investigating their genomic and transcriptomic implications: (i) enriching UCR annotation data, including ancestral genomes; (ii) exploring lncRNAs containing T-UCRs across pan-cancers; (iii) elucidating UCR involvement in regulatory elements; and (iv) analyzing population single-nucleotide variations linked to motifs, expression patterns, and diseases.
RESULTS: Our results indicate that, although a high number of protein-coding transcripts with UCRs (1,945 from 2,303), 1,775 contained UCRs outside CDS regions. Focusing on non-coding transcripts, 355 are mapped in 85 lncRNA genes, with 35 of them differentially expressed in at least one TCGA cancer type, seven lncRNAs strongly associated with survival time, and 23 differentially expressed according to single-cell cancer analysis. Additionally, we identified regulatory elements in 373 UCRs (77.5%), and found 353 SNP-UCRs (with at least 1% frequency) with potential regulatory effects, such as motif changes, eQTL potential, and associations with disease/traits. Finally, we identified 4 novel UCRs that had not been previously described.
CONCLUSION: This report compiles and organizes all the above information, providing new insights into the functional mechanisms of UCRs and their potential diagnostic applications.