Browsing by Author "Elfman, Justin"

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    The landscape of chimeric RNAs in non-diseased tissues and cells
    (Oxford University Press, 2020) Singh, Sandeep; Qin, Fujun; Kumar, Shailesh; Elfman, Justin; Lin, Emily; Pham, Lam-Phong; Yang, Amy; Li, Hui
    Chimeric RNAs and their encoded proteins have been traditionally viewed as unique features of neoplasia, and have been used as biomarkers and therapeutic targets for multiple cancers. Recent studies have demonstrated that chimeric RNAs also exist in non-cancerous cells and tissues, although large-scale, genome-wide studies of chimeric RNAs in non-diseased tissues have been scarce. Here, we explored the landscape of chimeric RNAs in 9495 non-diseased human tissue samples of 53 different tissues from the GTEx project. Further, we established means for classifying chimeric RNAs, and observed enrichment for particular classifications as more stringent filters are applied. We experimentally validated a subset of chimeric RNAs from each classification and demonstrated functional relevance of two chimeric RNAs in non-cancerous cells. Importantly, our list of chimeric RNAs in non-diseased tissues overlaps with some entries in several cancer fusion databases, raising concerns for some annotations. The data from this study provides a large repository of chimeric RNAs present in non-diseased tissues, which can be used as a control dataset to facilitate the identification of true cancer-specific chimeras.
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    UBA1-CDK16: A female-specific chimeric RNA emerging through evolution and involved in immune regulation
    (American Association for the Advancement of Science, 2026) Shi, Xinrui; Blackburn, Loryn; Singh, Sandeep; Glowczyk-Gluc, Martyna; Tajammal, Anam; Zahra, Shafaque; Kumar, Shailesh; Cornelison, Robert; Liang, Chen; Qin, Fujun; Liu, Aiqun; Lin, Shitong; Tang, Yue; Elfman, Justin; Manley, Thomas; Bullock, Timothy; Haverstick, Doris M.; Wu, Peng; Li, Hui
    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.