小分子RNA包括siRNAs、miRNAs和piRNAs业已被证明在机体的发育过程中起着广泛的调节作用。近年来的研究表明,microRNA(miRNA)途径参与调控果蝇生殖干细胞的增殖与分化,如Dcr-1,Loquacious以及AGO1蛋白等miRNA途径重要组分在决定干细胞命运中起关键作用,但其作用机制仍不清楚。
动物所陈大华研究组与Emory大学的金鹏实验室前期合作结果证明了miRNA途径另一个组分-dFmr1蛋白(编码果蝇的FMRP蛋白)也参与果蝇生殖干细胞的命运调控。为了阐明dFmr1介导的miRNA途径在果蝇生殖干细胞系统的作用机制,该研究中,作者采用免疫共沉淀的方法发现了一个名为Bantam的miRNA 小分子在卵巢中能够和dFMR1蛋白特异相结合。进一步研究作者发现,和dfmr1一样,bantam基因不仅是抑制原生殖细胞(PGCs)所必需的,它也是作为一个外源因子来维持生殖干细胞(GSCs)的自我更新。此外,作者发现bantam和dfmr1之间有遗传上的相互作用,并通过这种相互作用来调控GSCs的命运。本研究进一步证明了FMRP介导的翻译抑制通路是通过特定的小RNA分子起作用来调控干细胞的行为,相关成果发表在最近出版的PLoS Genet上。这项研究对揭示miRNA途径调控干细胞行为的机制具有重要的指导意义。(生物谷Bioon.com)
生物谷推荐原始出处:
PLoS Genet 5(4): e1000444. doi:10.1371/journal.pgen.1000444
The Bantam microRNA Is Associated with Drosophila Fragile X Mental Retardation Protein and Regulates the Fate of Germline Stem Cells
Yingyue Yang1#, Shunliang Xu2,3,4#, Laixin Xia1, Jun Wang1, Shengmei Wen1, Peng Jin2*, Dahua Chen1*
1 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China, 2 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America, 3 Department of Neurology, Second Hospital of Shandong University, Jinan, Shandong Province, People's Republic of China, 4 Department of Neurology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People's Republic of China
Fragile X syndrome, a common form of inherited mental retardation, is caused by the loss of fragile X mental retardation protein (FMRP). We have previously demonstrated that dFmr1, the Drosophila ortholog of the fragile X mental retardation 1 gene, plays a role in the proper maintenance of germline stem cells in Drosophila ovary; however, the molecular mechanism behind this remains elusive. In this study, we used an immunoprecipitation assay to reveal that specific microRNAs (miRNAs), particularly the bantam miRNA (bantam), are physically associated with dFmrp in ovary. We show that, like dFmr1, bantam is not only required for repressing primordial germ cell differentiation, it also functions as an extrinsic factor for germline stem cell maintenance. Furthermore, we find that bantam genetically interacts with dFmr1 to regulate the fate of germline stem cells. Collectively, our results support the notion that the FMRP-mediated translation pathway functions through specific miRNAs to control stem cell regulation.