Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis

被引:270
作者
Soper, Sarah F. C. [2 ]
van der Heijden, Godfried W. [1 ]
Hardiman, Tara C. [1 ]
Goodheart, Mary [3 ,4 ]
Martin, Sandra L. [5 ,6 ]
de Boer, Peter [7 ]
Bortvin, Alex [1 ]
机构
[1] Carnegie Inst Sci, Dept Embryol, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA
[3] MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA
[4] MIT, Dept Biol, Cambridge, MA 02142 USA
[5] Univ Colorado, Dept Cell & Dev Biol, Aurora, CO 80045 USA
[6] Univ Colorado, Program Mol Biol, Aurora, CO 80045 USA
[7] Radboud Univ Nijmegen, Med Ctr, Dept Obstet & Gynaecol, NL-6500 HB Nijmegen, Netherlands
关键词
D O I
10.1016/j.devcel.2008.05.015
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tight control of transposon activity is essential for the integrity of the germline. Recently, a germ-cell-specific organelle, nuage, was proposed to play a role in transposon repression. To test this hypothesis, we disrupted a murine homolog of a Drosophila nuage protein Maelstrom. Effects on male meiotic chromosome synapsis and derepression of transposable elements (TEs) were observed. In the adult Mael(-/-) testes, LINE-1 (L1) derepression occurred at the onset of meiosis. As a result, Mael(-/-) spermatocytes were flooded with L1 ribonucleoproteins (RNPs) that accumulated in large cytoplasmic enclaves and nuclei. Mael(-/-) spermatocytes with nuclear L1 RNPs exhibited massive DNA damage and severe chromosome asynapsis even in the absence of SP011-generated meiotic double-strand breaks. This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies the initiation of meiosis as an important step in TE control in the male germline.
引用
收藏
页码:285 / 297
页数:13
相关论文
共 55 条
[1]   A novel class of small RNAs bind to MILI protein in mouse testes [J].
Aravin, Alexei ;
Gaidatzis, Dimos ;
Pfeffer, Sebastien ;
Lagos-Quintana, Mariana ;
Landgraf, Pablo ;
Iovino, Nicola ;
Morris, Patricia ;
Brownstein, Michael J. ;
Kuramochi-Miyagawa, Satomi ;
Nakano, Toru ;
Chien, Minchen ;
Russo, James J. ;
Ju, Jingyue ;
Sheridan, Robert ;
Sander, Chris ;
Zavolan, Mihaela ;
Tuschl, Thomas .
NATURE, 2006, 442 (7099) :203-207
[2]   Small RNA guides for de novo DNA methylation in mammalian germ cells [J].
Aravin, Alexei A. ;
Bourc'his, Deborah .
GENES & DEVELOPMENT, 2008, 22 (08) :970-975
[3]   The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race [J].
Aravin, Alexei A. ;
Hannon, Gregory J. ;
Brennecke, Julius .
SCIENCE, 2007, 318 (5851) :761-764
[4]   Developmentally regulated piRNA clusters implicate MILI in transposon control [J].
Aravin, Alexei A. ;
Sachidanandam, Ravi ;
Girard, Angelique ;
Fejes-Toth, Katalin ;
Hannon, Gregory J. .
SCIENCE, 2007, 316 (5825) :744-747
[5]   Distribution of Atr protein in primary spermatocytes of a mouse chromosomal mutant: a comparison of preparation techniques [J].
Baart, EB ;
de Rooij, DG ;
Keegan, KS ;
de Boer, P .
CHROMOSOMA, 2000, 109 (1-2) :139-147
[6]   Progress in understanding the biology of the human mutagen LINE-1 [J].
Babushok, Daria V. ;
Kazazian, Haig H., Jr. .
HUMAN MUTATION, 2007, 28 (06) :527-539
[7]   Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11 [J].
Baudat, F ;
Manova, K ;
Yuen, JP ;
Jasin, M ;
Keeney, S .
MOLECULAR CELL, 2000, 6 (05) :989-998
[8]   Human LINE-1 retrotransposon induces DNA damage and apoptosis in cancer cells [J].
Belgnaoui, S. Mehdi ;
Gosden, Roger G. ;
Semmes, O. John ;
Haoudi, Abdelali .
CANCER CELL INTERNATIONAL, 2006, 6 (1)
[9]   SPO11 is required for sex-body formation, and Spo11 heterozygosity rescues the prophase arrest of Atm-/- spermatocytes [J].
Bellani, MA ;
Romanienko, PJ ;
Cairatti, DA ;
Camerini-Otero, RD .
JOURNAL OF CELL SCIENCE, 2005, 118 (15) :3233-3245
[10]   An atypical topoisomerase II from archaea with implications for meiotic recombination [J].
Bergerat, A ;
deMassy, B ;
Gadelle, D ;
Varoutas, PC ;
Nicolas, A ;
Forterre, P .
NATURE, 1997, 386 (6623) :414-417