Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis
Issued Date
2025-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85218193326
Journal Title
Nature Communications
Volume
16
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.16 No.1 (2025)
Suggested Citation
Funaguma S., Iida A., Saito Y., Tanboon J., De Los Reyes F.V., Sonehara K., Goto Y.I., Okada Y., Hayashi S., Nishino I. Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis. Nature Communications Vol.16 No.1 (2025). doi:10.1038/s41467-025-56567-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/105463
Title
Retrotrans-genomics identifies aberrant THE1B endogenous retrovirus fusion transcripts in the pathogenesis of sarcoidosis
Author's Affiliation
RIKEN Center for Integrative Medical Sciences
Siriraj Hospital
Graduate School of Medicine
Graduate School of Medicine
WPI Immunology Frontier Research Center, Osaka University
Osaka University
National Center for Global Health and Medicine
National Institute of Neuroscience, Kodaira
National Center of Neurology and Psychiatry
Siriraj Hospital
Graduate School of Medicine
Graduate School of Medicine
WPI Immunology Frontier Research Center, Osaka University
Osaka University
National Center for Global Health and Medicine
National Institute of Neuroscience, Kodaira
National Center of Neurology and Psychiatry
Corresponding Author(s)
Other Contributor(s)
Abstract
Transposon-like human element 1B (THE1B) originates from ancient retroviral sequences integrated into the primate genome approximately 50 million years ago, now accounting for at least 27,233 copies in the human genome, suggesting their extensive influence on human genomic architecture. Here we report identification of 19 THE1B fusion transcripts through short- and long-read RNA-seq analysis, 15 of which are previously unmapped, showing elevated expression in 16 individuals with sarcoid myopathy (SM), as compared to 400 controls with various other muscle diseases. Analysis of publicly available RNA-seq data indicated a correlation between the reduced expression of eight THE1B fusion transcripts and clinical improvement in individuals with cutaneous sarcoidosis receiving tofacitinib treatment. Single-cell or single-nucleus RNA-seq analyses of sarcoidosis not only confirmed these transcripts but also revealed a novel read-through transcript, SIRPB1-SIRPD, and TREM2.1, predominantly in granuloma-associated macrophages. The expression profiles of THE1B fusion transcripts in tuberculosis (TB) significantly differed from SM in single-cell RNA-seq data, suggesting that the differences between TB’s caseous granulomas and sarcoidosis’s non-caseous granulomas might be linked to disparate expression patterns of THE1B fusion transcripts. Our retrotrans-genomics approach has not only identified the genomic landscape of sarcoidosis but also provided new insights into its etiology.