Assessing the robustness of human ncRNA notations

The HUGO Gene Nomenclature Committee (HGNC) is the only worldwide authority that assigns standardised nomenclature to human genes (1). All studies related to the human genome and genes worldwide should adhere to HGNC-approved gene names and symbols, emphasizing the importance of precise classification and naming. Recent studies have revealed the functional and clinical relevance of RNU2-2P, which is linked to neurodevelopmental disorders and cancer (2–4), underscoring the need to reassess the classification of pseudogenes and functional non-coding RNA genes. In this study, we explore the conservation and expression of genes from 15 small ncRNA families, including U1, U2, U4, U5, U6, U4ATAC, U6ATAC, U11, U12, Vault tRNA (VTRNA), Y RNA, tRNA, 7SL, U7, and 7SK, to identify non-coding RNA-derived pseudogenes that are under strong negative selection in the human genome. Our findings highlight three highly conserved and expressed pseudogenes—RNU2-2P, RNU1-27P, and RNU1-28P—that are likely misclassified, as existing evidence suggests they may play a role in disease research. This warrants a reevaluation of their status as pseudogenes. Additionally, we identified RNU5F-1, a functional copy of RNU5, which is lowly conserved and expressed, yet its classification as a functional gene raises questions about its potential role. Furthermore, other pseudogenes and functional ncRNAs that could also be misclassified were identified, suggesting the necessity for further experimental and clinical examination.