title: Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi.
abstract: Fragile X syndrome (FraX), the most common form of inherited mental retardation, is caused by the absence of the evolutionally conserved fragile X mental retardation protein (FMRP). While neuronal functions of FMRP have been intensively studied for the last two decades, its role in non-neuronal cells remains poorly understood. Piwi, a key component of the Piwi-interacting RNA (piRNA) pathway, plays an essential role in germline development. In the present study, we report that similar to piwi, dfmr1, the Drosophila homolog of human FMR1, is required for transposon suppression in the germlines. Genetic analyses showed that dfmr1 and piwi act synergistically in heterochromatic silencing, and in inhibiting the differentiation of primordial germline cells and transposon expression. Northern analyses showed that roo piRNA expression levels are reduced in dfmr1 mutant ovaries, suggesting a role of dfmr1 in piRNA biogenesis. Biochemical analysis demonstrated a physical interaction between dFMRP and Piwi via their N-termini. Taken together, we propose that dFMRP cooperates with Piwi in maintaining genome integrity by regulating heterochromatic silencing in somatic cells and suppressing transposon activity via the piRNA pathway in germlines.
authors: State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Fangfang
authors: F
authors: Jiang
authors: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Falong
authors: F
authors: Lu
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Peixue
authors: P
authors: Li
authors: State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Science and Technology Center, Fenyang College, Shanxi Medical University, Shanxi 032200, China; Department of Medical Laboratory Science, Fenyang College, Shanxi Medical University, Shanxi 032200, China. Electronic address: weil998@sina.com.
authors: Wei
authors: W
authors: Liu
authors: State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Lu
authors: L
authors: Zhao
authors: State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qifu
authors: Q
authors: Wang
authors: State Key Laboratory of Plant Genomics and National Center for Plant Gene Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xiaofeng
authors: X
authors: Cao
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Lei
authors: L
authors: Zhang
authors: State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: yqzhang@genetics.ac.cn.
authors: Yong Q
authors: YQ
authors: Zhang
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000737:chemistry / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D049750:Genome, Insect; D009154:Mutation; D010053:Ovary / Q000254:growth & development; D010063:Ovum / Q000166:cytology; D063146:Polycomb-Group Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018626:Retroelements
chemical_list: D060565:Argonaute Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D018626:Retroelements; C467328:FMR1 protein, Drosophila; C452193:heterochromatin protein 1, Drosophila; C116498:piwi protein, Drosophila
keywords: FMRP; Fragile X syndrome; Germline; piRNA; piwi