Blockade of pachytene piRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity.
Blockade of pachytene piRNA biogenesis reveals a novel requirement for maintaining post-meiotic germline genome integrity.
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Pachytene PiRNA生物发生的阻断揭示了维持后寿命生殖基因组完整性的新需求。
DOI：
10.1371/journal.pgen.1003038
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Wang PJ
中科院分区：
文献类型：
--
作者：
Zheng K;Wang PJ
piwi相互作用rna是一类不同类型的小非编码rna，涉及转座元件的沉默和基因组完整性的保护。在哺乳动物中，雄性生殖细胞在减数分裂的粗期前期和粗期阶段分别表达两个遗传和发育上不同的pirna群体。粗粒前pirna主要来源于逆转录转座子，并且是它们沉默所必需的。相比之下，粗线素pirna起源于约3000个基因组簇，它们的生物发生和功能仍然是谜。在这里，我们报道了小鼠精母细胞中假定的RNA解旋酶MOV10L1的条件失活会导致粗线素piRNA的特异性丢失，粗线素piRNA前体转录物的显著积累，以及Piwi蛋白与线粒体的异常极性聚集。粗线蛋白pirna缺乏的精母细胞在减数分裂过程中没有LINE1逆转录转座子的抑制，但在减数分裂后的圆形精母细胞阶段受到阻滞，导致大量DNA损伤。我们的研究结果表明，MOV10L1在粗线蛋白piRNAs的初级加工中作用于Piwi蛋白的上游，并且表明，与粗线蛋白前piRNAs不同，粗线蛋白piRNAs在维持减数分裂后基因组完整性方面具有独特的功能。小的非编码rna在发育和疾病中发挥关键作用。生殖系基因组的完整性对后代的福祉和物种的生存至关重要。piwi相互作用rna （piRNAs）是一类小的非编码rna，在性腺中大量表达。与microrna和小干扰rna （sirna）相比，pirna的生物发生和功能仍然知之甚少。在这里，我们已经确定了MOV10L1，一种假定的RNA解旋酶，作为小鼠piRNA生物发生的主要调节剂。我们发现粗线素pirna的产生需要MOV10L1。粗线蛋白pirna的阻断破坏生殖细胞发育并导致减数分裂后基因组完整性的缺陷。因此，MOV10L1和其他piRNA通路组分的突变可能导致人类男性不育。
Piwi-interacting RNAs are a diverse class of small non-coding RNAs implicated in the silencing of transposable elements and the safeguarding of genome integrity. In mammals, male germ cells express two genetically and developmentally distinct populations of piRNAs at the pre-pachytene and pachytene stages of meiosis, respectively. Pre-pachytene piRNAs are mostly derived from retrotransposons and required for their silencing. In contrast, pachytene piRNAs originate from ∼3,000 genomic clusters, and their biogenesis and function remain enigmatic. Here, we report that conditional inactivation of the putative RNA helicase MOV10L1 in mouse spermatocytes produces a specific loss of pachytene piRNAs, significant accumulation of pachytene piRNA precursor transcripts, and unusual polar conglomeration of Piwi proteins with mitochondria. Pachytene piRNA–deficient spermatocytes progress through meiosis without derepression of LINE1 retrotransposons, but become arrested at the post-meiotic round spermatid stage with massive DNA damage. Our results demonstrate that MOV10L1 acts upstream of Piwi proteins in the primary processing of pachytene piRNAs and suggest that, distinct from pre-pachytene piRNAs, pachytene piRNAs fulfill a unique function in maintaining post-meiotic genome integrity. Small non-coding RNAs play critical roles during development and in disease. The integrity of the germline genome is of paramount importance to the wellbeing of offspring and the survival of species. Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs abundantly expressed in the gonad. Compared to microRNAs and small-interfering RNAs (siRNAs), the biogenesis and function of piRNAs remain poorly understood. Here we have identified MOV10L1, a putative RNA helicase, as a master regulator of piRNA biogenesis in mouse. We find that production of pachytene piRNAs requires MOV10L1. Blockade of pachytene piRNAs disrupts germ cell development and results in defects in post-meiotic genome integrity. Therefore, mutations in MOV10L1 and other piRNA pathway components may contribute to male infertility in humans.
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影响因子：
4.1
作者：
Chuma, Shinichiro;Hosokawa, Mihoko;Nakatsuji, Norio
通讯作者：
Nakatsuji, Norio
DOI：
10.1073/pnas.94.26.14602
发表时间：
1997-12-23
影响因子：
11.1
作者：
O'Gorman, S;Dagenais, NA;Marchuk, Y
通讯作者：
Marchuk, Y
影响因子：
11.4
作者：
Dalmay, T;Horsefield, R;Baulcombe, DC
通讯作者：
Baulcombe, DC
影响因子：
64.5
作者：
Brennecke, Julius;Aravin, Alexei A.;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
1.5
作者：
Inselman, Amy L.;Nakamura, Noriko;Brown, Paula R.;Willis, William D.;Goulding, Eugenia H.;Eddy, Edward M.
通讯作者：
Eddy, Edward M.