论文标题：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

期刊： Frontiers of Medicine

作者：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, Xiaojian Sun

发表时间：15 Jun 2023

DOI：10.1007/s11684-022-0968-4

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导 读

上海交通大学医学院附属瑞金医院陈赛娟院士、黄金艳研究员、吴哲褒教授、孙晓建研究员等在Frontiers of Medicine联合发表了研究论文《通过对LU结构域蛋白家族的系统分析发现人类新基因LY6A编码小鼠Ly-6A/Sca-1的同源蛋白并且在垂体瘤中异常表达》(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)。本文通过对人和小鼠中LU结构域蛋白质的系统搜索与比较基因组研究，发现了人类新基因LY6A，其编码小鼠Ly-6ASca-1的同源蛋白并且在垂体瘤中异常表达，且在基因、蛋白结构、转录调控等方面具有重要特征，为研究基因调控和进化机制提供了模型。

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.

含有Ly-6和uPAR（LU）结构域的蛋白质构成了一类庞大的细胞表面标志物家族。其中，小鼠Ly-6A/Sca-1是多种干细胞中广泛使用的标志物，但其在人类中的直系同源物尚未明确。本研究基于对小鼠和人类LU结构域蛋白的系统性调查和比较基因组学研究，发现了一个此前未被注释的人类基因，该基因编码小鼠Ly-6A/Sca-1的候选直系同源物。该基因被命名为LY6A，其大部分外显子序列与一个长链非编码RNA（lncRNA）基因反向重叠。研究发现，LY6A在垂体肿瘤中异常表达，而在正常垂体组织中不表达，这表明它可能与肿瘤发生相关。与小鼠Ly-6A/Sca-1类似，人类LY6A的表达也受干扰素上调，提示人类和小鼠之间存在保守的转录调控机制。我们克隆了LY6A的全长cDNA，其编码的蛋白序列、结构域组成和外显子-内含子结构均与小鼠Ly-6A/Sca-1高度保守。LY6A蛋白在细胞中的异位表达表明，其在加工过程和糖基磷脂酰肌醇（GPI）锚定至细胞膜的功能上与小鼠Ly-6A/Sca-1一致。综上所述，这些研究揭示了一个新的人类基因，其编码的蛋白可能作为候选生物标志物，并为研究基因调控和进化机制提供了一个有趣的模型基因。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

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

作者

Dan Liu^1,2, Chunhui Xu³, Yanting Liu⁴, Wen Ouyang¹, Shaojian Lin⁴, Aining Xu¹, Yuanliang Zhang¹, Yinyin Xie¹, Qiuhua Huang¹, Weili Zhao¹, Zhu Chen¹, Lan Wang³, Saijuan Chen¹, Jinyan Huang^1,5, Zhe Bao Wu^4,6, Xiaojian Sun¹

机构

1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

2. Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China

3. CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China

4. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

5. Biomedical Big Data Center, First Affiliated Hospital, Zhejiang University School of Medicine, and Cancer Center, Zhejiang University, Hangzhou 310000, China

6. Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

通讯作者

Saijuan Chen, Jinyan Huang, Zhe Bao Wu, Xiaojian Sun

引用这篇文章

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, Xiaojian Sun. 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. Front. Med., 2023, 17(3): 458–475 https://doi.org/10.1007/s11684-022-0968-4

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-022-0968-4

https://link.springer.com/article/10.1007/s11684-022-0968-4

感谢作者对Frontiers of Medicine的信任和支持。

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