RNA干擾(RNAi)是一種在真核生物中保守的基因表達調控機制。RNAi的效應復合體的核心是一種能結合小分子RNA的Argonaute蛋白。擬南芥擁有10個Argonaute蛋白和大量不同類型的小分子RNAs。這些小分子RNAs進入Argonaute蛋白復合體是否具有選擇性和這種選擇性由什么因子決定尚不為人所知。戚益軍實驗室純化了四個Argonaute蛋白復合物,并對各復合物中的小分子RNA組分進行了大規模序列分析。分析表明不同Argonaute結合的小分子RNAs具有不同的5’末端核苷酸偏好性,比如AGO1結合以U起始的小分子RNAs,而AGO2主要結合以A起始的小分子RNAs。進一步的體外和體內實驗證實不同的Argonaute對5’末端核苷酸不同的小分子RNAs的結合活性存在很大差異。改變小分子RNA的5’末端核苷酸可以使小分子RNA進入錯誤的Argonaute蛋白,并改變其生物學功能。戚益軍博士實驗室的這一發現表明,小分子RNA的序列本身決定了小分子RNA的zui終進入哪個Argonaute蛋白并行使其功能。同時該發現也意味著Argonaute蛋白結合小分子RNA的結構域的進化參與了它們功能的特異化,也為植物micrornAs 5’末端為尿嘧啶的進化動力提供了解釋。
密士軍博士和蔡濤博士是該文章的共同*作者,論文的其他作者還有胡玉剛,陳葉苗,倪方銳,武亮,李姍,龍承祖,陳涉和冷泉港實驗室的Emily Hodges和Greg Hannon博士。戚益軍博士為本文的通訊作者。此項研究為科技部863項目和北京市科委資助課題,在北京生命科學研究所完成。(來源:北京生命科學研究所)
生物谷推薦原始出處:
(Cell),doi:10.1016/j.cell.2008.02.034,Shijun Mi, Tao Cai, Yijun Qi
Sorting of Small rnas into ArABIdopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide
Shijun Mi1, 3, Tao Cai1, 3, Yugang Hu1, Yemiao Chen1, Emily Hodges2, Fangrui Ni1, Liang Wu1, Shan Li1, Huanyu Zhou1, Chengzu Long1, She Chen1, Gregory J. Hannon2 and Yijun Qi1, CellsRNA進入蛋白具有選擇性, CellsRNA進入蛋白具有選擇性
1National Institute of Biological sciences, No.7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
2Cold Spring Harbor Laboratory, Watson School of Biological Sciences, and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
Received 1 November 2007; revised 4 January 2008; accepted 15 February 2008. Published online: March 13, 2008. Available online 13 March 2008.
Summary
Argonaute (AGO) proteins recruit small RNAs to form the core of RNAi effector complexes. Arabidopsis encodes ten AGO proteins and a large network of small RNAs. How these small RNAs are sorted into specific AGO complexes remains largely unknown. We have cataloged small RNAs resident in four AGO complexes. We found that AGO2 and AGO4 preferentially recruit small RNAs with a 5′ terminal adenosine, whereas AGO1 harbors microRNAs (miRNAs) that favor a 5′ terminal uridine. AGO5 predominantly binds small RNAs that initiate with cytosine. Changing the 5′ terminal nucleotide of an miRNA predictably redirected it into a different AGO complex and alters its biological activity. These results reveal a role for small RNA sequences in assorting among AGO complexes. This suggests that specialization of AGO complexes might involve remodeling the 5′ end-binding pocket to accept certain small RNA sequences, perhaps explaining the evolutionary drive for miRNAs to initiate with uridine.
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