RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans
RNA interference and retinoblastoma-related genes are required for repression of endogenous siRNA targets in Caenorhabditis elegans
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DOI：
10.1073/pnas.0810589105
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发表时间：
2008-12-23
影响因子：
11.1
通讯作者：
Sharp, Phillip A.
中科院分区：
文献类型：
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作者：
Grishok, Alla;Hoersch, Sebastian;Sharp, Phillip A.
在秀丽隐杆线虫中，最近发现了大量的内源性短RNA，对应于数千个基因。这一发现表明，除了沉默病毒和转座子外，这些短干扰RNA（siRNA）可能有助于调节许多发育和其他信号通路。在这里，我们提出了一个基因表达的微阵列分析RNA干扰（RNAi）相关的突变体rde-4，zfp-1，和alg-1和视网膜母细胞瘤（Rb）突变体lin-35。我们发现，Dicer复合物RDE-4和染色质相关锌指蛋白ZFP-1的一个组成部分，不涉及内源性RNAi，调节重叠的基因组。值得注意的是，基因a）在rde-4和zfp-1突变体中上调和B）在lin-35（Rb）突变体中上调，但下调的基因在具有相应内源siRNA（endo-siRNA）的基因组中高度表达。我们的研究表明，内源性SiRNA与染色质因子（无论是C.急性淋巴细胞白血病-1（ALL-1）的直系同源物，来自染色体10（AF 10），ZFP-1，或肿瘤抑制基因Rb的融合基因，以调节重叠的基因组，并预测基于RNAi的染色质沉默在C.优雅的。
In Caenorhabditis elegans, a vast number of endogenous short RNAs corresponding to thousands of genes have been discovered recently. This finding suggests that these short interfering RNAs (siRNAs) may contribute to regulation of many developmental and other signaling pathways in addition to silencing viruses and transposons. Here, we present a microarray analysis of gene expression in RNA interference (RNAi)-related mutants rde-4, zfp-1, and alg-1 and the retinoblastoma (Rb) mutant lin-35. We found that a component of Dicer complex RDE-4 and a chromatin-related zinc finger protein ZFP-1, not implicated in endogenous RNAi, regulate overlapping sets of genes. Notably, genes a) up-regulated in the rde-4 and zfp-1 mutants and b) up-regulated in the lin-35(Rb) mutant, but not the down-regulated genes are highly represented in the set of genes with corresponding endogenous siRNAs (endo-siRNAs). Our study suggests that endogenous siRNAs cooperate with chromatin factors, either C. elegans ortholog of acute lymphoblastic leukemia-1 (ALL-1)-fused gene from chromosome 10 (AF10), ZFP-1, or tumor suppressor Rb, to regulate overlapping sets of genes and predicts a large role for RNAi-based chromatin silencing in control of gene expression in C. elegans.