MOV10L1 is necessary for protection of spermatocytes against retrotransposons by Piwi-interacting RNAs

被引：162

作者：

Frost, Robert J. A. ^{[1
]}

Hamra, F. Kent ^{[2
]}

Richardson, James A. ^{[1
,3
]}

Qi, Xiaoxia ^{[1
]}

Bassel-Duby, Rhonda ^{[1
]}

Olson, Eric N. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 26期

基金：

美国国家卫生研究院;

关键词：

RNA helicase; Armitage; meiosis; GERM; PROTEIN; EXPRESSION; ELEMENTS; CHAMP; MILI; GENE;

D O I：

10.1073/pnas.1007158107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Piwi-interacting RNAs (piRNAs) comprise a broad class of small non-coding RNAs that function as an endogenous defense system against transposable elements. Here we show that the putative DExD-box helicase MOV10-like-1 (MOV10L1) is essential for silencing retrotransposons in the mouse male germline. Mov10l1 is specifically expressed in germ cells with increasing expression from gonocytes/type A spermatogonia to pachytene spermatocytes. Primary spermatocytes of Mov10l1(-/-) mice show activation of LTR and LINE-1 retrotransposons, followed by cell death, causing male infertility and a complete block of spermatogenesis at early prophase of meiosis I. Despite the early expression of Mov10l1, germline stem cell maintenance appears unaffected in Mov10l1(-/-) mice. MOV10L1 interacts with the Piwi proteins MILI and MIWI. MOV10L1 also interacts with heat shock 70-kDa protein 2 (HSPA2), a testis-enriched chaperone expressed in pachytene spermatocytes and also essential for male fertility. These studies reveal a crucial role of MOV10L1 in male fertility and piRNA-directed retrotransposon silencing in male germ cells and suggest that MOV10L1 functions as a key component of a safeguard mechanism for the genetic information in male germ cells of mammals.

引用

页码：11847 / 11852

页数：6

共 28 条

[1]

Ahmed EA, 2009, METHODS MOL BIOL, V558, P263, DOI 10.1007/978-1-60761-103-5_16

[2] Small RNA Silencing Pathways in Germ and Stem Cells [J].

Aravin, A. A. ;

Hannon, G. J. .

CONTROL AND REGULATION OF STEM CELLS, 2008, 73 :283-290

[3] 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

[4] 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

[5] Hot L1s account for the bulk of retrotransposition in the human population [J].

Brouha, B ;

Schustak, J ;

Badge, RM ;

Lutz-Prigget, S ;

Farley, AH ;

Moran, JV ;

Kazazian, HH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (09) :5280-5285

[6] Plzf is required in adult male germ cells for stem cell self-renewal [J].

Buaas, FW ;

Kirsh, AL ;

Sharma, M ;

McLean, DJ ;

Morris, JL ;

Griswold, MD ;

de Rooij, DG ;

Braun, RE .

NATURE GENETICS, 2004, 36 (06) :647-652

[7] MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline [J].

Carmell, Michelle A. ;

Girard, Angelique ;

van de Kant, Henk J. G. ;

Bourc'his, Deborah ;

Bestor, Timothy H. ;

de Rooij, Dirk G. ;

Hannon, Gregory J. .

DEVELOPMENTAL CELL, 2007, 12 (04) :503-514

[8] Oligozoospermia and heat-shock protein expression in ejaculated spermatozoa [J].

Cedenho, A. P. ;

Lima, S. B. ;

Cenedeze, M. A. ;

Spaine, D. M. ;

Ortiz, V. ;

Oehninger, S. .

HUMAN REPRODUCTION, 2006, 21 (07) :1791-1794

[9] The impact of retrotransposons on human genome evolution [J].

Cordaux, Richard ;

Batzer, Mark A. .

NATURE REVIEWS GENETICS, 2009, 10 (10) :691-703

[10] miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis [J].

Deng, W ;

Lin, HF .

DEVELOPMENTAL CELL, 2002, 2 (06) :819-830

← 1 2 3 →