Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi. Issue 1 (20th January 2016)

• Record Type: Journal Article
• Authors: Jiang, Fangfang; Lu, Falong; Li, Peixue; Liu, Wei; Zhao, Lu; Wang, Qifu; Cao, Xiaofeng; Zhang, Lei; Zhang, Yong Q.
• Is Part Of: Journal of genetics and genomics. Volume 43:Issue 1(2016)
• Page Start: 11
• Page End: 24
• Publication Date: 2016-01-20
• Subjects: Fragile X syndrome -- FMRP -- piwi -- piRNA -- Germline; co-IP co-immunoprecipitation -- dfmr1 Drosophila fragile X mental retardation 1 -- dFMRP Drosophila fragile X mental retardation protein -- FMR1 fragile X mental retardation 1 -- FMRP fragile X mental retardation protein -- FraX Fragile X syndrome -- GFP green fluorescent protein -- GSC germline stem cell -- HP1 heterochromatin protein 1 -- LTR long terminal repeat -- miRNA microRNA -- PBS phosphate buffered saline -- PBST phosphate buffered saline with Triton X-100 -- PcG Polycomb group -- PEV position effect variegation -- PGC primordial germ cell -- piRNA Piwi-interacting RNA -- RT-PCR reverse transcription-polymerase chain reaction -- SEM standard error of the mean; Genetics -- Periodicals; Genomics -- Periodicals; 576.505
• DOI: 10.1016/j.jgg.2015.11.001
• Languages: English
• ISSNs: 1673-8527

Abstract

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.