The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression.
The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression.
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DOI：
10.1016/j.devcel.2013.11.014
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发表时间：
2013-12-23
影响因子：
11.8
通讯作者：
Mello, Craig C.
中科院分区：
文献类型：
--
作者：
Seth, Meetu;Shirayama, Masaki;Gu, Weifeng;Ishidate, Takao;Conte, Darryl, Jr.;Mello, Craig C.
生物体可以通过重新表达引导基因沉默的病原体特异性小rna来发展适应性序列特异性免疫。例如，秀丽隐杆线虫PIWI-Argonaute/piRNA通路将RNA依赖的RNA聚合酶RdRP招募到外源序列，以扩增跨代小RNA诱导的表观遗传沉默信号（称为RNAe）。我们提供的证据表明，除了沉默序列的适应性记忆外，秀丽隐杆线虫还可以对表达/自身mrna形成相反的适应性记忆。我们将这种可以阻止或逆转RNAe的机制称为rna诱导的表观遗传基因激活（RNAa）。我们发现CSR-1参与rdrp扩增的小rna与种系表达mrna互补，是RNAa所必需的。我们发现具有RNAa活性的转基因也表现出同源的CSR-1小rna的积累。我们的研究结果表明，秀丽隐杆线虫适应性地获得并维持了识别和保护自身mrna的跨代CSR-1记忆，使pirna无需事先暴露就能识别外来序列。
Organisms can develop adaptive sequence-specific immunity by re-expressing pathogen-specific small RNAs that guide gene silencing. For example, the C. elegans PIWI-Argonaute/piRNA pathway recruits RNA-dependent RNA polymerase RdRP to foreign sequences to amplify a trans-generational small RNA-induced epigenetic silencing signal (termed RNAe). Here we provide evidence that in addition to an adaptive memory of silenced sequences, C. elegans can also develop an opposing adaptive memory of expressed/self mRNAs. We refer to this mechanism, which can prevent or reverse RNAe as RNA-induced epigenetic gene activation (RNAa). We show that CSR-1, which engages RdRP-amplified small RNAs complementary to germline-expressed mRNAs, is required for RNAa. We show that a transgene with RNAa activity also exhibits accumulation of cognate CSR-1 small RNAs. Our findings suggest that C. elegans adaptively acquires and maintains a trans-generational CSR-1 memory that recognizes and protects self mRNAs, allowing piRNAs to recognize foreign sequences innately, without need for prior exposure.
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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：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
影响因子：
64.8
作者：
Buckley, Bethany A.;Burkhart, Kirk B.;Gu, Sam Guoping;Spracklin, George;Kershner, Aaron;Fritz, Heidi;Kimble, Judith;Fire, Andrew;Kennedy, Scott
通讯作者：
Kennedy, Scott
影响因子：
64.5
作者：
Conine CC;Moresco JJ;Gu W;Shirayama M;Conte D Jr;Yates JR 3rd;Mello CC
通讯作者：
Mello CC
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