耶鲁林海帆Cell子刊文章

　　

耶鲁林海帆Cell子刊文章

生物通报道，近期耶鲁大学医学院干细胞研究中心和日本京都大学交叉医学研究所发育与分化实验室的研究小组在最新的Cell子刊《Current Biology》上发表最新研究进展Mili Interacts with Tudor Domain-Containing Protein 1 in Regulating Spermatogenesis。

 

文章通讯作者，领导这一研究项目的是来自耶鲁大学医学院的顶级学者林海帆教授，干细胞领域杰出的华人科学家。

 

在生殖细胞系的发育过程中piwi蛋白具有重要的作用，对干细胞自我更新，表观遗传学调控，转录沉默都具有重要意义。Piwi蛋白与一类经典的非编码RNA（ncRNA）结合，它与piwi蛋白结合的ncRNA叫piwiRNA（简称piRNA）。哺乳动物的piwi蛋白如Mili主要分布在精原细胞的细胞浆中，与精原细胞中的特殊细胞器如nuage，derivative有关联。

 

在本研究中林海帆研究小组发现Mili能特异性地与Tudor domain-containing protein 1（Tdrd1）结合。Mili的N端能与Tdrd1的N端结合发生作用，促进精子发生，并且这一调节过程不依赖piRNA的作用。

 

这些结果表明，Mili可与Tdrd1直接作用，不依赖于piRNA，且这一调节模式对精子的发生而言具有重要的意义。

（生物通 小茜）

生物通推荐原文检索：Mili Interacts with Tudor Domain-Containing Protein 1 in Regulating Spermatogenesis

Jianquan Wang1,Jonathan P. Saxe1,Takashi Tanaka2,Shinichiro Chuma2andHaifan Lin1,,

1 Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA

2 Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

 

【ummary】

Piwi proteins are essential for germline development, stem cell self-renewal, epigenetic regulation, and transposon silencing [1,2,3,4,5,6,7]. They bind to a complex class of small noncoding RNAs called Piwi-interacting RNAs (piRNAs) [8]. Mammalian Piwi proteins such as Mili are localized in the cytoplasm of spermatogenic cells, where they are associated with a germline-specific organelle called the nuage or its derivative, the chromatoid body, as well as with polysomes [9]. To investigate the molecular mechanisms mediated by Mili, we searched for Mili-interacting proteins. Here, we report that Mili specifically interacts with Tudor domain-containing protein 1 (Tdrd1), a germline protein that contains multiple Tudor domains [10,11]. This RNA-independent interaction is mediated through the N-terminal domain of Mili and the N-terminal region of Tdrd1 containing the myeloid Nervy DEAF-1 (MYND) domain and the first two Tudor domains. In addition, Mili positively regulates the expression of the Tdrd1 mRNA. Furthermore, Mili andTdrd1 mutants share similar spermatogenic defects. However, Tdrd1, unlike Mili, is not required for piRNA biogenesis.Our results suggest that Mili interacts with Tdrd1 in the nuage and chromatoid body. This interaction does not contribute to piRNA biogenesis but representsa regulatory mechanism that is critical for spermatogenesis.