遗传 ›› 2018, Vol. 40 ›› Issue (2): 87-94.doi: 10.16288/j.yczz.17-255

• 综述 •    下一篇

脆性X智力低下蛋白参与非编码RNA通路的研究进展

李恩惠1(),赵欣1,张策1,刘威2()   

  1. 1. 山西医科大学生理学系，太原 030001
    2. 山西医科大学汾阳学院医学检验系，汾阳 032200
  • 收稿日期:2017-11-07 修回日期:2018-01-05 出版日期:2018-02-20 发布日期:2018-01-11
  • 作者简介:作者简介: 李恩惠,硕士研究生,专业方向：神经生理学。E-mail: 674515106@qq.com|通讯作者: 刘威,博士,副教授,研究方向：发育生物学。E-mail: liuwei@sxmu.edu.cn
  • 基金资助:
    国家自然科学基金(31501175);山西医科大学汾阳学院科技发展重点基金项目(2018C02)

Fragile X mental retardation protein participates in non-coding RNA pathways

Enhui Li1(),Xin Zhao1,Ce Zhang1,Wei Liu2()   

  1. 1. Department of Physiology, Shanxi Medical University, Taiyuan 030001, China
    2. Department of Examination, Fenyang College of Shanxi Medical University, Fenyang 032200, China
  • Received:2017-11-07 Revised:2018-01-05 Online:2018-02-20 Published:2018-01-11
  • Supported by:
    the National Natural Science Foundation of China(31501175);Key Developing Program for Science and Technique of Shanxi Medical University Fenyang College(2018C02)

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摘要：

脆性X综合征(Fragile X syndrome)是一种最常见的遗传性智力低下疾病,并且伴有语言和行为障碍等。该疾病是由脆性X智力低下基因(Fragile X mental retardation 1, FMR1)突变而导致脆性X智力低下蛋白(Fragile X mental retardation protein, FMRP)表达异常造成的。近年来,研究发现FMRP参与非编码RNA通路,并发挥多种重要生物学功能,这对理解脆性X综合征发病机理具有重要的推动作用。首先发现FMRP与siRNA和miRNA通路中Dicer酶、Ago1和Ago2蛋白相互作用,参与神经活动及生殖干细胞命运决定等重要过程。随后又发现FMRP与piRNA通路中Aub、Ago1和Piwi蛋白相互作用,维持了染色体正常结构和基因组稳定性。最新研究结果发现FMRP与lncRNA相互作用,其功能和价值正引起关注。本文从FMRP与非编码RNA通路的关系展开,着重介绍了FMRP与piRNA之间的相互作用,以期为深入理解非编码RNA通路在脆性X综合征的发病过程中作用提供参考,同时期望与临床医学领域尽快形成交叉研究,早日促进理论成果转化为临床应用。

关键词: FMRP, 非编码RNA通路, piRNA, 基因组稳定, 果蝇

Abstract:

Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells. Subsequent studies showed that the Drosophila FMRP participates in piRNA pathway by interacting with Aub, Ago1 and Piwi in the maintenance of normal chromatin structures and genomic stability. More recent studies showed that FMRP is associated with lncRNA pathway, suggesting a potential role for the involvement in the clinical manifestations. In this review, we summarize the novel findings and explore the relationship between FMRP and non-coding RNA pathways, particularly the piRNA pathway, thereby providing critical insights on the molecular pathogenesis of Fragile X syndrome, and potential translational applications in clinical management of the disease.

Key words: FMRP, non-coding RNA pathway, piRNA, genome integrity, Drosophila