Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice
Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice
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DOI：
10.15252/embj.201386855
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发表时间：
2014-09-17
期刊：
影响因子：
11.4
通讯作者：
Bortvin, Alex
中科院分区：
文献类型：
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作者：
Castaneda, Julio;Genzor, Pavol;Bortvin, Alex
粗线期piRNA是在成年小鼠睾丸的精子细胞中丰富的一类Piwi相互作用的小RNA。它们通过一种知之甚少的机制从皮尔纳初级转录物加工而成，并且与胎儿转座子衍生的piRNA不同，它们在精子细胞转录组中缺乏互补靶标。我们报告了一种保守的皮尔纳途径蛋白Maelstrom（MAEL）的免疫纯化复合物富含MIWI（粗线期piRNA的Piwi伴侣）、Tudor结构域蛋白和粗线期皮尔纳初级转录物的加工中间体。我们提供了这些复合物在Mael（129）基因敲除小鼠中的功能意义的证据，这些小鼠表现出精子发生停滞，伴有顶体和鞭毛畸形。Mael（129）缺失突变体睾丸具有低水平的源自MAEL相关皮尔纳前体的piRNA，并且表现出许多生精mRNA（包括编码顶体和鞭毛蛋白的那些）的翻译减少。单倍体圆形精子细胞中的这些翻译缺陷可能是间接的，因为MAEL和皮尔纳前体都不与多聚核糖体相关，并且它们可能由粗线期piRNA和MIWI之间的不平衡引起。
Pachytene piRNAs are a class of Piwi-interacting small RNAs abundant in spermatids of the adult mouse testis. They are processed from piRNA primary transcripts by a poorly understood mechanism and, unlike fetal transposon-derived piRNAs, lack complementary targets in the spermatid transcriptome. We report that immunopurified complexes of a conserved piRNA pathway protein Maelstrom (MAEL) are enriched in MIWI (Piwi partner of pachytene piRNAs), Tudor-domain proteins and processing intermediates of pachytene piRNA primary transcripts. We provide evidence of functional significance of these complexes in Mael(129) knockout mice that exhibit spermiogenic arrest with acrosome and flagellum malformation. Mael(129)-null mutant testes possess low levels of piRNAs derived from MAEL-associated piRNA precursors and exhibit reduced translation of numerous spermiogenic mRNAs including those encoding acrosome and flagellum proteins. These translation defects in haploid round spermatids are likely indirect, as neither MAEL nor piRNA precursors associate with polyribosomes, and they may arise from an imbalance between pachytene piRNAs and MIWI.