GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins.

GTSF1 accelerates target RNA cleavage by PIWI-clade Argonaute proteins.
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DOI:
10.1038/s41586-022-05009-0
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发表时间:
2022-08
期刊:
影响因子:
64.8
通讯作者:
Zamore, Phillip D.
Zamore, Phillip D.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arif, Amena;Bailey, Shannon;Izumi, Natsuko;Anzelon, Todd A.;Ozata, Deniz M.;Andersson, Cecilia;Gainetdinov, Ildar;MacRae, Ian J.;Tomari, Yukihide;Zamore, Phillip D.

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Argonaute蛋白使用核酸向导来寻找和结合特定的DNA或RNA靶序列。Argonaute蛋白具有不同的生物学功能,并且许多保留了它们的祖先核糖核酸内切酶活性,切割靶核苷酸t10和t11之间的磷酸二酯键。在动物中,PIWI蛋白-一种专门的Argonaute蛋白-使用21-35个核苷酸的PIWI相互作用RNA(piRNA)来指导转座子沉默,保护种系基因组,并在配子发生期间调节基因表达。几乎所有动物的一种或两种性别的生育力都需要皮尔纳途径。皮尔纳的产生和功能都需要PIWI蛋白催化的RNA切割。小鼠和其他胎盘哺乳动物的精子发生需要三种不同的、发育调节的PIWI蛋白:MIWI(PIWIL 1)、MILI(PIWIL 2)和MIWI 2(PIWIL 4)。MIWI和MILI的piRNA引导的核糖核酸内切酶活性对于功能性精子的产生至关重要。小鼠和昆虫中的piRNA介导的沉默还需要GTSF 1,一种功能未知的PIWI相关蛋白。在这里,我们报告说,GTSF 1增强弱,内在的,piRNA指导的RNA裂解活动的PIWI蛋白,转化成有效的内切核糖核酸酶。因此,GTSF 1是增强Argonaute蛋白的催化活性的辅助蛋白的实例。进化上保守的RNA结合蛋白GTSF 1及其同源物与Argonaute蛋白的PIWI类成员相互作用,提高PIWI蛋白的RNA切割活性的效率,这是动物界的一项基本功能。
Argonaute proteins use nucleic acid guides to find and bind specific DNA or RNA target sequences. Argonaute proteins have diverse biological functions and many retain their ancestral endoribonuclease activity, cleaving the phosphodiester bond between target nucleotides t10 and t11. In animals, the PIWI proteins—a specialized class of Argonaute proteins—use 21–35 nucleotide PIWI-interacting RNAs (piRNAs) to direct transposon silencing, protect the germline genome, and regulate gene expression during gametogenesis. The piRNA pathway is required for fertility in one or both sexes of nearly all animals. Both piRNA production and function require RNA cleavage catalysed by PIWI proteins. Spermatogenesis in mice and other placental mammals requires three distinct, developmentally regulated PIWI proteins: MIWI (PIWIL1), MILI (PIWIL2) and MIWI2 (PIWIL4). The piRNA-guided endoribonuclease activities of MIWI and MILI are essential for the production of functional sperm. piRNA-directed silencing in mice and insects also requires GTSF1, a PIWI-associated protein of unknown function. Here we report that GTSF1 potentiates the weak, intrinsic, piRNA-directed RNA cleavage activities of PIWI proteins, transforming them into efficient endoribonucleases. GTSF1 is thus an example of an auxiliary protein that potentiates the catalytic activity of an Argonaute protein. The evolutionarily conserved RNA-binding protein GTSF1 and its homologues interact with members of the PIWI class of Argonaute proteins, increasing the efficiency of the RNA-cleaving activity of PIWI proteins, an essential function across the animal kingdom.
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Asterix/Gtsf1 连接反转录转座子的 tRNA 和 piRNA 沉默。
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