Paternal knockdown of tRNA (cytosine-5-)-methyltransferase (Dnmt2) increases offspring susceptibility to infection in flour beetles
Paternal knockdown of tRNA (cytosine-5-)-methyltransferase (Dnmt2) increases offspring susceptibility to infection in flour beetles
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DOI：
10.1101/2020.12.15.422063
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
N. Schulz;M. F. D. Buhr;J. Kurtz
中科院分区：
文献类型：
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作者：
N. Schulz;M. F. D. Buhr;J. Kurtz
在不同的生物体中，越来越多地报道了从父亲到后代的代际效应，但其潜在机制往往是未知的。在赤拟谷盗Tribolium castaneum中证明了父代跨代免疫启动（TGIP）：父代的非感染性细菌暴露（启动）可保护其后代至少两代免受感染性挑战。在这里，我们研究了Dnmt 2基因（在人类中重命名为Trdmt 1）的潜在作用，该基因编码一种高度保守的酶，该酶可甲基化一组tRNA的特定胞嘧啶，并且先前已报道参与小鼠的代际表观遗传。我们首先研究了基因表达，发现Dnmt 2在整个生命过程中都有表达，在睾丸中有高表达。敲低Dnmt 2在父亲减慢后代幼虫发育和增加死亡率的成年后代细菌感染后。然而，所观察到的效果是独立的父启动处理。总之，我们的研究结果指向Dnmt 2的作用，父亲的影响，而父亲的免疫启动背后的机制需要进一步的研究。
Intergenerational effects from fathers to offspring are increasingly reported in diverse organisms, but the underlying mechanisms are often unknown. Paternal trans-generational immune priming (TGIP) was demonstrated in the red flour beetle Tribolium castaneum: non-infectious bacterial exposure (priming) of fathers protects their offspring against an infectious challenge for at least two generations. Here we studied a potential role of the Dnmt2 gene (renamed as Trdmt1 in humans), which encodes a highly conserved enzyme that methylates specific cytosines of a set of tRNAs and has previously been reported to be involved in intergenerational epigenetic inheritance in mice. We first studied gene expression and found that Dnmt2 was expressed throughout life, with high expression in testes. Knockdown of Dnmt2 in fathers slowed down offspring larval development and increased mortality of the adult offspring upon bacterial infection. However, the observed effects were independent of the paternal priming treatment. In conclusion, our results point towards a role of Dnmt2 for paternal effects, while elucidation of the mechanisms behind paternal immune priming needs further studies.