Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi

Fangfang Jiang^a,
Falong Lu^b,
Peixue Li^c,
Wei Liu^{a, d, e
, ,},
Lu Zhao^a,
Qifu Wang^a,
Xiaofeng Cao^b,
Lei Zhang^c,
Yong Q. Zhang^{a
, ,}

a.
State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
b.
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
c.
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
d.
Science and Technology Center, Fenyang College, Shanxi Medical University, Shanxi 032200, China
e.
Department of Medical Laboratory Science, Fenyang College, Shanxi Medical University, Shanxi 032200, China

More Information

Corresponding author: E-mail address: weil998@sina.com (Wei Liu); E-mail address: yqzhang@genetics.ac.cn (Yong Q. Zhang)

摘要

- /
- /
- /
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 thatdfmr1 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.
- Fragile X syndrome /
- FMRP /
- piRNA /
- Germline

HTML全文

参考文献(51)

[1]	Alpatov, R., Lesch, B.J., Nakamoto-Kinoshita, M. et al. A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response Cell, 157 (2014),pp. 869-881
[2]	Anand, A., Kai, T. EMBO J., 31 (2012),pp. 870-882
[3]	Aravin, A.A., Klenov, M.S., Vagin, V.V. et al. Mol. Cell. Biol., 24 (2004),pp. 6742-6750
[4]	, Mukherjee, N., Bandaru, P., Miller, J.B. et al. FMRP targets distinct mRNA sequence elements to regulate protein expression Nature, 492 (2012),pp. 382-386
[5]	Bantignies, F., Grimaud, C., Lavrov, S. et al. Genes Dev., 17 (2003),pp. 2406-2420
[6]	Bozzetti, M.P., Specchia, V., Cattenoz, P.B. et al. J. Cell Sci., 128 (2015),pp. 2070-2084
[7]	Callan, M.A., Cabernard, C., Heck, J. et al. Hum. Mol. Genet., 19 (2010),pp. 3068-3079
[8]	Caudy, A.A., Myers, M., Hannon, G.J. et al. Fragile X-related protein and VIG associate with the RNA interference machinery Genes Dev., 16 (2002),pp. 2491-2496
[9]	Chambeyron, S., Popkova, A., Payen-Groschene, G. et al. Proc. Natl. Acad. Sci. USA, 105 (2008),pp. 14964-14969
[10]	Costa, A., Wang, Y., Dockendorff, T.C. et al. Dev. Cell, 8 (2005),pp. 331-342
[11]	Cox, D.N., Chao, A., Baker, J. et al. Genes Dev., 12 (1998),pp. 3715-3727
[12]	Cox, D.N., Chao, A., Lin, H. Development, 127 (2000),pp. 503-514
[13]	Crawford, D.C., Schwartz, C.E., Meadows, K.L. et al. Survey of the fragile X syndrome CGG repeat and the short-tandem-repeat and single-nucleotide-polymorphism haplotypes in an African American population Am. J. Hum. Genet., 66 (2000),pp. 480-493
[14]	Deshpande, G., Calhoun, G., Schedl, P. Genetics, 174 (2006),pp. 1287-1298
[15]	Dockendorff, T.C., Su, H.S., McBride, S.M. et al. Neuron, 34 (2002),pp. 973-984
[16]	Ephrussi, B., Herold, J.L. Genetics, 29 (1944),pp. 148-175
[17]	Epstein, A.M., Bauer, C.R., Ho, A. et al. Dev. Biol., 330 (2009),pp. 83-92
[18]	Grimaud, C., Bantignies, F., Pal-Bhadra, M. et al. RNAi components are required for nuclear clustering of Polycomb group response elements Cell, 124 (2006),pp. 957-971
[19]	Ishizuka, A., Siomi, M.C., Siomi, H. Genes Dev., 16 (2002),pp. 2497-2508
[20]	Iwasaki, Y.W., Siomi, M.C., Siomi, H. PIWI-interacting RNA: its biogenesis and functions Annu. Rev. Biochem., 84 (2015),pp. 405-433
[21]	James, T.C., Elgin, S.C. Mol. Cell. Biol., 6 (1986),pp. 3862-3872
[22]	Jin, P., Zarnescu, D.C., Ceman, S. et al. Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway Nat. Neurosci., 7 (2004),pp. 113-117
[23]	Lin, H., Spradling, A.C. Development, 124 (1997),pp. 2463-2476
[24]	Lin, H., Yue, L., Spradling, A.C. Development, 120 (1994),pp. 947-956
[25]	Liu, B., Li, P., Li, X. et al. Plant Physiol., 139 (2005),pp. 296-305
[26]	Liu, T., Wan, R.P., Tang, L.J. et al. Mol. Neurobiol., 51 (2015),pp. 1053-1063
[27]	Liu, W., Jiang, F., Bi, X. et al. Hum. Mol. Genet., 21 (2012),pp. 4655-4668
[28]	Livak, K.J., Schmittgen, T.D. Methods, 25 (2001),pp. 402-408
[29]	Megosh, H.B., Cox, D.N., Campbell, C. et al. Curr. Biol., 16 (2006),pp. 1884-1894
[30]	Oostra, B.A., Willemsen, R. Biochim. Biophys. Acta, 1790 (2009),pp. 467-477
[31]	Pal-Bhadra, M., Leibovitch, B.A., Gandhi, S.G. et al. Science, 303 (2004),pp. 669-672
[32]	Ramos, A., Hollingworth, D., Adinolfi, S. et al. The structure of the N-terminal domain of the fragile X mental retardation protein: a platform for protein–protein interaction Structure, 14 (2006),pp. 21-31
[33]	Ross, R.J., Weiner, M.M., Lin, H. PIWI proteins and PIWI-interacting RNAs in the soma Nature, 505 (2014),pp. 353-359
[34]	Saito, K., Inagaki, S., Mituyama, T. et al. Nature, 461 (2009),pp. 1296-1299
[35]	Saito, K., Nishida, K.M., Mori, T. et al. Genes Dev., 20 (2006),pp. 2214-2222
[36]	Santoro, M.R., Bray, S.M., Warren, S.T. Molecular mechanisms of fragile X syndrome: a twenty-year perspective Annu. Rev. Pathol., 7 (2012),pp. 219-245
[37]	Schulze, S.R., Wallrath, L.L. Annu. Rev. Entomol., 52 (2007),pp. 171-192
[38]	Sweeney, S.J., Campbell, P., Bosco, G. Genetics, 178 (2008),pp. 1311-1325
[39]	Tessier, C.R., Broadie, K. Neurobiol. Dis., 41 (2011),pp. 147-159
[40]	Thomson, T., Lin, H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect Annu. Rev. Cell Dev. Biol., 25 (2009),pp. 355-376
[41]	Vagin, V.V., Sigova, A., Li, C. et al. A distinct small RNA pathway silences selfish genetic elements in the germline Science, 313 (2006),pp. 320-324
[42]	Wallrath, L.L., Elgin, S.C. Genes Dev., 9 (1995),pp. 1263-1277
[43]	Xu, T., Rubin, G.M. Development, 117 (1993),pp. 1223-1237
[44]	Xu, X.L., Li, Y., Wang, F. et al. J. Neurosci., 28 (2008),pp. 11883-11889
[45]	Yang, Y., Xu, S., Xia, L. et al. PLoS Genet., 5 (2009),p. e1000444
[46]	Zamparini, A.L., Davis, M.Y., Malone, C.D. et al. Development, 138 (2011),pp. 4039-4050
[47]	Zhang, L., Ren, F., Zhang, Q. et al. The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control Dev. Cell, 14 (2008),pp. 377-387
[48]	Zhang, W., Cheng, Y., Li, Y. et al. Hum. Mol. Genet., 23 (2014),pp. 5188-5196
[49]	Zhang, Y.Q., Bailey, A.M., Matthies, H.J. et al. Cell, 107 (2001),pp. 591-603
[50]	Zhang, Y.Q., Broadie, K. Fathoming fragile X in fruit flies Trends Genet., 21 (2005),pp. 37-45
[51]	Zhu, C.H., Xie, T. Development, 130 (2003),pp. 2579-2588