UBA1-CDK16: A Female-Specific Chimeric RNA Emerging Through Evolution and Involved in Immune Regulation

ABSTRACT: Chimeric RNAs resulting from intergenic splicing represent a novel mechanism for transcriptome expansion. To explore the role of this new layer of the transcriptome in sex-specific immunity, we analyzed RNA-seq data from 425 blood samples and identified the first female-specific chimeric RNA, UBA1-CDK16, which was further validated in over 1,200 blood samples. This chimeric RNA forms via cis-splicing between two adjacent X-linked parental genes, UBA1 and CDK16, despite both being expressed in both sexes. We demonstrated that a female-specific chromatin loop at the UBA1-CDK16 junction sites facilitates the intergenic splicing. Evolutionary analysis revealed that UBA1-CDK16 became female-specific in humans through at least two independent paths. Functional studies suggested UBA1-CDK16 is enriched in the myeloid lineage and may regulate myeloid cell development and inflammatory responses. Notably, its abnormal expression in female COVID-19 patients correlates with altered neutrophil counts, highlighting its potential role in disease pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311311 | GEO | 2026/04/20

REPOSITORIES: GEO