A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

Abstract

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

Keywords

LU domain-containing protein family / novel human gene / LY6A / pituitary tumor / biomarker / nonsynonymous SNP / GPI-anchored protein

References

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Acknowledgements

This work was supported by the National Key Research and Development Plan of China (No. 2018YFA0107802 to Xiaojian Sun, Nos. 2018YFA0107200 and 2018YFA0800203 to Lan Wang), the General Program of the National Natural Science Foundation of China (Nos. 81470316 and 81670094 to Xiaojian Sun, No. 81972339 to Zhe Bao Wu, Nos. 81570122 and 81770205 to Jinyan Huang, Nos. 81670122 and 81970150 to Lan Wang), the National Research Center for Translational Medicine (Shanghai) grant (No. NRCTM (SH)-2019-05 to Zhe Bao Wu), the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (No. 20152506 to Xiaojian Sun), Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research (No. 2019CXJQ01 to Saijuan Chen and Xiaojian Sun), Innovative Research Team of High-level Local Universities in Shanghai (to Weili Zhao and Xiaojian Sun), the Samuel Waxman Cancer Research Foundation, and the Shanghai Guangci Translational Medical Research Development Foundation.

Compliance with ethics guidelines

Dan Liu, Chunhui Xu, Yanting Liu, Wen Ouyang, Shaojian Lin, Aining Xu, Yuanliang Zhang, Yinyin Xie, Qiuhua Huang, Weili Zhao, Zhu Chen, Lan Wang, Saijuan Chen, Jinyan Huang, Zhe Bao Wu, and Xiaojian Sun declare no potential conflicts of interest. All the procedure of this study was approved by the Institutional Review Board of the Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

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