Li En-Hui, Zhao Xin, Zhang Ce, Liu Wei
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Department of Examination, Fenyang College of Shanxi Medical University, Fenyang 032200, China.
Yi Chuan. 2018 Feb 20;40(2):87-94. doi: 10.16288/j.yczz.17-255.
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.
脆性X综合征是最常见的遗传性智力障碍形式之一。它由脆性X智力低下1（FMR1）基因突变引起，导致脆性X智力低下蛋白（FMRP）缺失或异常表达。最近的研究表明，FMRP参与非编码RNA途径，并在生理学中发挥各种重要作用，从而扩展了我们对脆性X综合征发病机制的认识。初步研究表明，果蝇FMRP通过与Dicer、Ago1和Ago2相互作用参与siRNA和miRNA途径，涉及神经活动和生殖系干细胞的命运决定。随后的研究表明，果蝇FMRP通过与Aub、Ago1和Piwi相互作用参与piRNA途径，以维持正常的染色质结构和基因组稳定性。最近的研究表明，FMRP与lncRNA途径相关，提示其可能参与临床表现。在本综述中，我们总结了新发现，并探讨了FMRP与非编码RNA途径之间的关系，特别是piRNA途径，从而为脆性X综合征的分子发病机制提供关键见解，以及在该疾病临床管理中的潜在转化应用。
