<i>UBA1-CDK16</i> : A female-specific chimeric RNA emerging through evolution and involved in immune regulation
Chimeric RNAs resulting from intergenic splicing represent a distinct mechanism for transcriptome expansion. To explore the role of this previously unidentified layer of the transcriptome in sex-specific immunity, we analyzed RNA sequencing data from 425 blood samples and identified a female-specific chimeric RNA, UBA1-CDK16 , which was further validated in more than 1200 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 that UBA1-CDK16 is enriched in the myeloid lineage and may regulate myeloid cell development. Notably, its abnormal expression in female patients with COVID-19 correlates with altered neutrophil counts, highlighting its potential role in the disease progression.
Authors
- Shafaque Zahra
- Fujun Qin (ORCID: https://orcid.org/0000-0003-2337-7137)
- Justin Elfman (ORCID: https://orcid.org/0000-0003-0516-5325)
- Yue Tang (ORCID: https://orcid.org/0000-0002-2519-4505)
- Shitong Lin (ORCID: https://orcid.org/0000-0002-0737-2785)
- Robert Cornelison (ORCID: https://orcid.org/0000-0002-9775-6677)
- Anam Tajammal (ORCID: https://orcid.org/0009-0005-8206-3420)
- Chen Liang (ORCID: https://orcid.org/0000-0002-4510-2014)
- TIMOTHY BULLOCK
- Martyna Glowczyk-Gluc
- Doris M. Haverstick
- Sandeep Singh
- Aiqun Liu
- Shailesh Kumar (ORCID: https://orcid.org/0000-0002-1872-9903)
- Thomas Manley (ORCID: https://orcid.org/0009-0002-3040-7496)
- Xinrui Shi (ORCID: https://orcid.org/0009-0003-1739-8895)
- Peng Wu (ORCID: https://orcid.org/0000-0003-4498-7663)
- Hui Li (ORCID: https://orcid.org/0000-0002-7879-1792)
- Loryn Blackburn (ORCID: https://orcid.org/0000-0002-2001-873X)
Institutions
- Shanxi Agricultural University (CN)
- Cincinnati Children's Hospital Medical Center (US)
- Union Hospital (HK)
- Zhengzhou University (CN)
- National Institute of Plant Genome Research (IN)
- Tumor Hospital of Guangxi Medical University (CN)
- Tongji Hospital (CN)
- Bridge Pharma (United States) (US)
- Huazhong University of Science and Technology (CN)
- University of Virginia (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-05-29
- DOI
- https://doi.org/10.1126/sciadv.adz9784
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of General Medical Sciences