A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality.
A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality.
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DOI：
10.1038/nature11352
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发表时间：
2012-09-20
期刊：
影响因子：
64.8
通讯作者：
Kennedy, Scott
中科院分区：
文献类型：
--
作者：
Buckley, Bethany A.;Burkhart, Kirk B.;Gu, Sam Guoping;Spracklin, George;Kershner, Aaron;Fritz, Heidi;Kimble, Judith;Fire, Andrew;Kennedy, Scott
表观遗传信息经常在每一代开始时被删除。然而，在某些情况下，表观遗传信息可以从父母传递给后代（表观遗传）。表观遗传的一个特别突出的例子是C. elegans，这可以继承超过五代。为了理解这一过程，我们对有缺陷的动物进行了遗传筛选，以将RNAi沉默信号传递给后代。该筛选鉴定了基因遗传性RNAi缺陷（hrde）-1。hrde-1编码Argonaute（Ago），其与暴露于dsRNA的动物后代的生殖细胞中的小干扰（si）RNA相关。在这些生殖细胞的细胞核中，HRDE-1参与Nrde核RNAi途径，将H3 K9 me 3引导至RNAi靶向的基因组位点并促进RNAi遗传。在正常生长条件下，HRDE-1与内源性表达的siRNA结合，其指导生殖细胞中的核基因沉默。在hrde-1或核RNAi缺陷动物中，种系沉默随着世代时间而丧失。同时，这些动物在配子形成和功能方面表现出不断恶化的缺陷，最终导致不育。这些结果确定Ago HRDE-1指导生殖细胞核中的基因沉默事件，其驱动多代RNAi遗传并促进生殖细胞谱系的永生。我们建议C.线虫使用RNAi遗传机制将过去世代积累的表观遗传信息传递给后代，以调节重要的生物过程。
Epigenetic information is frequently erased near the start of each new generation. In some cases, however, epigenetic information can be transmitted from parent to progeny (epigenetic inheritance). A particularly striking example of epigenetic inheritance is dsRNA-mediated gene silencing (RNAi) in C. elegans, which can be inherited for more than five generations. To understand this process we conducted a genetic screen for animals defective for transmitting RNAi silencing signals to future generations. This screen identified the gene heritable RNAi defective (hrde)-1. hrde-1 encodes an Argonaute (Ago) that associates with small interfering (si)RNAs in germ cells of the progeny of animals exposed to dsRNA. In nuclei of these germ cells, HRDE-1 engages the Nrde nuclear RNAi pathway to direct H3K9me3 at RNAi targeted genomic loci and promote RNAi inheritance. Under normal growth conditions, HRDE-1 associates with endogenously expressed siRNAs, which direct nuclear gene silencing in germ cells. In hrde-1 or nuclear RNAi deficient animals, germline silencing is lost over generational time. Concurrently, these animals exhibit steadily worsening defects in gamete formation and function that ultimately lead to sterility. These results establish that the Ago HRDE-1 directs gene-silencing events in germ cell nuclei, which drive multi-generational RNAi inheritance and promote immortality of the germ cell lineage. We propose that C. elegans uses the RNAi inheritance machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.
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影响因子：
64.5
作者：
Ashe A;Sapetschnig A;Weick EM;Mitchell J;Bagijn MP;Cording AC;Doebley AL;Goldstein LD;Lehrbach NJ;Le Pen J;Pintacuda G;Sakaguchi A;Sarkies P;Ahmed S;Miska EA
通讯作者：
Miska EA
影响因子：
64.5
作者：
Tabara, H;Yigit, E;Mello, CC
通讯作者：
Mello, CC
DOI：
10.1073/pnas.1113310108
发表时间：
2011-12-06
影响因子：
11.1
作者：
Burton, Nick O.;Burkhart, Kirk B.;Kennedy, Scott
通讯作者：
Kennedy, Scott
影响因子：
4.5
作者：
Burkhart KB;Guang S;Buckley BA;Wong L;Bochner AF;Kennedy S
通讯作者：
Kennedy S
DOI：
10.1126/science.1157647
发表时间：
2008-07-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Guang S;Bochner AF;Pavelec DM;Burkhart KB;Harding S;Lachowiec J;Kennedy S
通讯作者：
Kennedy S