專題:Cell專題
在基因組中除了DNA和RNA序列以外,還有許多調控基因的信息,它們雖然本身不改變基因的序列,但是可以通過基因修飾,蛋白質與蛋白質、DNA和其它分子的相互作用,而影響和調節遺傳的基因的功能和特性,並且通過細胞分裂和增殖周期影響遺傳,這就是表觀遺傳學(epigenetics)。
在表觀遺傳學研究中,小分子RNAs(Short interfering RNAs,siRNAs)可以引導DNA甲基化,以及異染色質組蛋白修飾,導致序列特異性轉錄基因沉默。這一路徑稱為RNA介導的DNA甲基化路徑(RNA-directed DNA methylation,簡稱RdDM)。
在本研究中,研究人員鑑定了一個RdDM的效應器(RdDM effector),KTF1。KTF1發生功能性喪失的突變會導致DNA甲基化程度變小,並釋放出沉默RdDM轉座子的siRNA,促進沉默RdDM路徑。KTF1與轉錄延伸因子(transcription elongation factor)SPT5相似,其C端富含GWWG重複序列。
KTF1與ARGONAUTE4(AGO4)一起定位在核心位置,並與AGO4和RNA轉錄因子結合。
研究結果表明,KTF1是一個銜接蛋白,它同時連結AGO4和Pol V產生的轉錄因子網路,AGO4結合到siRNA,以上的分子結合在一起形成RdDM效應複合物。這種複合效應器的特徵是具有雙重的結合作用,同時結合AGO4和轉錄因子。(生物谷Bioon.com)
生物谷推薦原始出處:
Cell, Volume 137,1 May 2009 doi:10.1016/j.cell.2009.04.028
An Effector of RNA-Directed DNA Methylation in Arabidopsis Is an ARGONAUTE 4- and RNA-Binding Protein
Xin-Jian He1,6,Yi-Feng Hsu1,3,6,Shihua Zhu1,4,Andrzej T. Wierzbicki5,Olga Pontes5,Craig S. Pikaard5,Hai-Liang Liu1,Co-Shine Wang3,Hailing Jin2andJian-Kang Zhu1,,
1 Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA 92521, USA
2 Institute for Integrative Genome Biology and Department of Plant Pathology, University of California, Riverside, Riverside, CA 92521, USA
3 Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan
4 College of Science and Technology, Ningbo University, Ningbo 315211, China
5 Biology Department, Washington University, Campus Box 1137, One Brookings Drive, St. Louis, MO 63130, USA
6 These authors contributed equally to this work
DNA methylation is a conserved epigenetic mark inplants and mammals. In Arabidopsis, DNA methylation can be triggered by small interfering RNAs (siRNAs) through an RNA-directed DNA methylation (RdDM) pathway. Here, we report the identification of an RdDM effector, KTF1. Loss-of-function mutations in KTF1 reduce DNA methylation and release the silencing of RdDM target loci without abolishing the siRNA triggers. KTF1 has similarity to the transcription elongation factor SPT5 and contains a C-terminal extension rich in GW/WG repeats. KTF1 colocalizes with ARGONAUTE 4 (AGO4) in punctate nuclear foci and binds AGO4 and RNA transcripts. Our results suggest KTF1 as an adaptor protein that binds scaffold transcripts generated by Pol V and recruits AGO4 and AGO4-bound siRNAs to form an RdDM effector complex. The dual interaction of an effector protein with AGO and small RNA target transcripts may bea general feature of RNA-silencing effector complexes.