A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis.
A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis.
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MIWI/piRNA 在小鼠精子发生过程中的翻译激活功能
DOI：
10.1016/j.cell.2019.11.022
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发表时间：
2019-12-12
期刊：
影响因子：
64.5
通讯作者：
Liu MF
中科院分区：
文献类型：
--
作者：
Dai P;Wang X;Gou LT;Li ZT;Wen Z;Chen ZG;Hua MM;Zhong A;Wang L;Su H;Wan H;Qian K;Liao L;Li J;Tian B;Li D;Fu XD;Shi HJ;Zhou Y;Liu MF
精子发生是一个高度协调的发育过程，在此过程中，染色质浓缩使转录从翻译中分离出来。生精mRNAs转录较早，并在需要翻译之前储存在一种非活性的惰性状态;然而，在精子发生过程中，这些被抑制的mRNAs如何被激活仍不清楚。我们先前报道了MIWI/皮尔纳机制负责在精子发生后期准备精子生产过程中的mRNA消除。在这里，我们意外地发现，同样的机制也负责激活精子发生mRNA的一个子集的翻译，以协调形态转化为精子。这种作用需要piRNA与靶mRNA在其3′ UTR中的特异性碱基配对相互作用，这通过与顺式作用富含AU的元件偶联来激活翻译，从而以发育阶段特异性方式使MIWI/皮尔纳/eIF 3f/HuR超复合物的形成成核。这些发现揭示了皮尔纳系统在翻译激活中的关键作用，我们表明这是精子细胞发育所需的功能。皮尔纳途径通过与HuR和eIF 3f的功能性相互作用，在小鼠精子发生期间一组特定mRNA的翻译激活中起重要作用。
Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3′ UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development. The piRNA pathway, through functional interplay with HuR and eIF3f, plays an important role in translational activation of a specific set of mRNAs during mouse spermiogenesis.
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通讯作者：
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