A pre-mRNA-associating factor links endogenous siRNAs to chromatin regulation.
A pre-mRNA-associating factor links endogenous siRNAs to chromatin regulation.
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DOI：
10.1371/journal.pgen.1002249
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发表时间：
2011-08
期刊：
影响因子：
4.5
通讯作者：
Kennedy S
中科院分区：
文献类型：
--
作者：
Burkhart KB;Guang S;Buckley BA;Wong L;Bochner AF;Kennedy S
在植物和真菌中，小RNA通过建立抑制性染色质状态来沉默细胞核中的基因表达。内源性小RNA在后生动物细胞核中的作用在很大程度上是未知的。在这里，我们表明，内源性小干扰RNA（endo-siRNA）直接组蛋白H3赖氨酸9甲基化（H3 K9 me）在秀丽隐杆线虫。此外，我们报告了核RNAi缺陷（nrde）-1和nrde-4的鉴定和表征。Endo-siRNA驱动的H3 K9 me需要核RNAi途径，包括Argonaute（Ago）NRDE-3、保守的核RNAi因子NRDE-2以及NRDE-1和NRDE-4。小RNA指导NRDE-1与RNAi靶向的基因的前mRNA和染色质结合。NRDE-3和NRDE-2是NRDE-1与前mRNA和染色质结合所必需的。NRDE-4是NRDE-1/染色质结合所必需的，但不是NRDE-1/前mRNA结合所必需的。这些数据表明，NRDE-1是一种新的前mRNA和染色质相关因子，将小RNA与H3 K9甲基化联系起来。此外，这些结果表明，在C.优美的染色质由DNA和蛋白质组成。染色质可以以许多不同的状态存在。染色质的状态受到高度调节，以确保基因正确表达。RNA在染色质的调控中起着重要的作用。例如，在植物和真菌中，小RNA驱动异染色质（一种抑制性染色质状态）的形成。在动物细胞中已经鉴定出许多类型的小RNA，但这些小RNA的功能在很大程度上是未知的。利用线虫C.作为一个模型系统，我们确定了一个小RNA途径，调节染色质的状态。我们报告的两个新的因素，称为NRDE-1和NRDE-4，这在这个核小RNA通路的行为的鉴定。NRDE-1和NRDE-4将小RNA与染色质调控联系起来。此外，我们表明，内源性表达的小RNA，称为endo-siRNA，指导组蛋白的翻译后修饰，这是染色质的核心组成部分。这些结果建立了小RNA和动物染色质调控之间的直接联系。
In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA–driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans. Chromatin consists of DNA and proteins. Chromatin can exist in many different states. The state of chromatin in highly regulated in order to ensure that genes are expressed correctly. RNAs play an important role in the regulation of chromatin. For example, in plants and fungi small RNAs drive the formation of heterochromatin, a repressive chromatin state. Many types of small RNAs have been identified in animal cells, but the functions of these small RNAs are largely unknown. Using the nematode C. elegans as a model system, we identified a small RNA pathway that regulates the state of chromatin. We report the identification of two new factors, termed NRDE-1 and NRDE-4, which act in this nuclear small RNA pathway. NRDE-1 and NRDE-4 link small RNAs to chromatin regulation. Additionally, we show that endogenously expressed small RNAs, termed the endo-siRNAs, direct the post-translational modification of histone proteins, which are core components of chromatin. These results establish a direct connection between small RNAs and chromatin regulation in animals.
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影响因子：
64.5
作者：
Halic M;Moazed D
通讯作者：
Moazed D
影响因子：
4
作者：
Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. 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
影响因子：
16.8
作者：
Janowski, Bethany A.;Huffman, Kenneth E.;Corey, David R.
通讯作者：
Corey, David R.
影响因子：
11.4
作者：
Aoki, Kazuma;Moriguchi, Hiromi;Tabara, Hiroaki
通讯作者：
Tabara, Hiroaki