Ubiquitin meets PIWI protein.
Ubiquitin meets PIWI protein.
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DOI：
10.1038/aja.2013.19
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发表时间：
2013-05
影响因子：
2.9
通讯作者：
I. Nagamori;T. Nakano
中科院分区：
文献类型：
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作者：
I. Nagamori;T. Nakano
MIWI和PIWI相互作用RNA（皮尔纳）与PIWI家族成员（包括MIWI）结合，参与精子发生的转录后调控，但其分子功能尚不清楚。最近，Zhao及其同事报道，将皮尔纳加载到MIWI导致晚期精子细胞中泛素-蛋白酶体介导的降解，并且该过程对于晚期精子细胞成熟为精子至关重要。本文对MIWI的功能以及皮尔纳与PIWI家族成员在精子发生中的相互作用提出了新的见解。在精子发生的晚期（即精子发生），染色质通过过渡蛋白将组蛋白替换为鱼精蛋白而变得紧密堆积。这一过程对于生育力的投降是必不可少的，并且不仅带来动态的染色质变化，而且还带来全局转录抑制。转录后调节对于该过程至关重要，并且涉及PIWI蛋白质家族。PIWI家族是从果蝇到人类的许多生物中生殖细胞发育所必需的保守基因家族。PIWI家族蛋白在PIWI相互作用RNA（piRNA）的产生中起关键作用，piRNA是生殖细胞特异性的小RNA子集，其有助于转录和转录后基因抑制，推测是通过piRNA的功能。1在三个小鼠PIWI家族成员（MIWI、MILI和MIWI 2）中，MILI和MIWI 2已被报道通过诱导从头DNA甲基化（推测是通过胚胎睾丸中的piRNA）在逆转录转座子的基因沉默中发挥重要作用。最近，Zhao及其同事发现piRNA通过APC/C蛋白酶体途径诱导MIWI的泛素化和降解，并且泛素化介导的MIWI降解对于精子发生是必不可少的。2本研究对MIWI的调控及其在精子发生中的作用有了新的认识。
MIWI and PIWI-interacting RNA (piRNA), which binds to PIWI family members including MIWI, contribute to post-transcriptional regulation in spermiogenesis, however, their molecular functions had been unclear. Recently, Zhao and colleagues reported that loading of piRNA to MIWI leads to ubiquitin-proteasome mediated degradation in late spermatid and that this process is essential for the maturation from late spermatid to sperm. This paper casts a novel insight on the function of MIWI and the interaction between piRNA and the PIWI family member in spermatogenesis. In the late stage of spermatogenesis (ie, spermiogensis), chromatin becomes tightly packed by the replacement of histones to protamines via transition proteins. This process is essential for the capitulation of fertility and brings about not only dynamic chromatin changes but also global transcription suppression. Post-transcriptional regulation is critical for this process and involves the PIWI family of proteins. The PIWI family is a conserved gene family essential for germ cell development in many organisms ranging fromDrosophila to humans. PIWI family proteins play crucial roles in the production of PIWI-interacting RNAs (piRNAs), a germ cell-specific subset of small RNAs that contribute to transcriptional and post-transcriptional gene suppression, presumably through the function of piRNAs. 1 Among three mouse PIWI family members (MIWI, MILI and MIWI2), MILI and MIWI2 have been reported to play essential roles in the gene silencing of retrotransposons by inducing de novo DNA methylation, presumably via piRNAs in embryonic testes. In contrast, the molecular function of MIWI, required for spermiogenesis, remains largely unknown.Recently, Zhao and colleagues showed that piRNAs induce the ubiquitination and degradation of MIWI through the APC/C proteasome pathway and that ubiquitinationmediated MIWI degradation is essential to spermiogenesis. 2 This study casts new insight on the regulation of MIWI and its role in spermiogenesis.