The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation
The Mouse Cytosine-5 RNA Methyltransferase NSun2 Is a Component of the Chromatoid Body and Required for Testis Differentiation
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DOI：
10.1128/mcb.01523-12
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发表时间：
2013-04-01
影响因子：
5.3
通讯作者：
Frye, Michaela
中科院分区：
文献类型：
--
作者：
Hussain, Shobbir;Tuorto, Francesca;Frye, Michaela
转录后调控机制是精子发生过程中蛋白质合成的关键，通常由类染色体组成。在这里，我们将RNA甲基转移酶NSUN2确定为类染色体的一个新成分，并进一步表明NSUN2是小鼠睾丸生殖细胞分化所必需的。在NSUN2缺失的睾丸中，编码Ddx4、Miwi和Tudor结构域(TDR)蛋白的基因受到抑制，表明RNA加工和转录后通路受损。NSUN2的缺失特别阻止了生殖细胞减数分裂进入粗线期，因为精原细胞和支持细胞在基因敲除的小鼠中不受影响。当我们同时缺失NSUN2和DNMT2时，我们观察到了相同的表型，DNMT2是迄今为止唯一鉴定的另一种胞嘧啶-5 RNA甲基转移酶，表明在精原干细胞或支持细胞中，DNMT2与NSUN2在功能上不是多余的。当NSUN2和DNMT2两种甲基转移酶缺失时，特异性的NSUN2和DNMT2甲基化tRNAs的数量减少，这表明RNA甲基化途径在雄性生殖细胞分化中起着重要作用。
Posttranscriptional regulatory mechanisms are crucial for protein synthesis during spermatogenesis and are often organized by the chromatoid body. Here, we identify the RNA methyltransferase NSun2 as a novel component of the chromatoid body and, further, show that NSun2 is essential for germ cell differentiation in the mouse testis. In NSun2-depleted testes, genes encoding Ddx4, Miwi, and Tudor domain-containing (Tdr) proteins are repressed, indicating that RNA-processing and posttranscriptional pathways are impaired. Loss of NSun2 specifically blocked meiotic progression of germ cells into the pachytene stage, as spermatogonial and Sertoli cells were unaffected in knockout mice. We observed the same phenotype when we simultaneously deleted NSun2 and Dnmt2, the only other cytosine-5 RNA methyltransferase characterized to date, indicating that Dnmt2 was not functionally redundant with NSun2 in spermatogonial stem cells or Sertoli cells. Specific NSun2- and Dnmt2-methylated tRNAs decreased in abundance when both methyltransferases were deleted, suggesting that RNA methylation pathways play an essential role in male germ cell differentiation.