2008年3月13日,，北京生命科學(xué)研究所戚益軍博士實(shí)驗(yàn)室在Cell雜志以Immediate Early Publication形式在線發(fā)表題為“Sorting of Small RNAs into Arabidopsis Argonaute Complexes is Directed by the 5’ Terminal Nucleotide”的文章 (www.cell.com),。該文報(bào)道了在模式植物擬南芥中,小分子RNA 5’末端核苷酸對(duì)其進(jìn)入不同的Argonaute蛋白復(fù)合體起到?jīng)Q定作用。
RNA干擾（RNAi）是一種在真核生物中保守的基因表達(dá)調(diào)控機(jī)制,。RNAi的效應(yīng)復(fù)合體的核心是一種能結(jié)合小分子RNA的Argonaute蛋白。擬南芥擁有10個(gè)Argonaute蛋白和大量不同類型的小分子RNAs,。這些小分子RNAs進(jìn)入Argonaute蛋白復(fù)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(shí)驗(yàn)室純化了四個(gè)Argonaute蛋白復(fù)合物，并對(duì)各復(fù)合物中的小分子RNA組分進(jìn)行了大規(guī)模序列分析,。分析表明不同Argonaute結(jié)合的小分子RNAs具有不同的5’末端核苷酸偏好性,，比如AGO1結(jié)合以U起始的小分子RNAs，而AGO2主要結(jié)合以A起始的小分子RNAs,。進(jìn)一步的體外和體內(nèi)實(shí)驗(yàn)證實(shí)不同的Argonaute對(duì)5’末端核苷酸不同的小分子RNAs的結(jié)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(jìn)入錯(cuò)誤的Argonaute蛋白，并改變其生物學(xué)功能,。戚益軍博士實(shí)驗(yàn)室的這一發(fā)現(xiàn)表明,，小分子RNA的序列本身決定了小分子RNA的最終進(jìn)入哪個(gè)Argonaute蛋白并行使其功能。同時(shí)該發(fā)現(xiàn)也意味著Argonaute蛋白結(jié)合小分子RNA的結(jié)構(gòu)域的進(jìn)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(jìn)化動(dòng)力提供了解釋,。
密士軍博士和蔡濤博士是該文章的共同第一作者,，論文的其他作者還有胡玉剛，陳葉苗,，倪方銳,，武亮，李?yuàn)?，龍承祖,，陳涉和冷泉港?shí)驗(yàn)室的Emily Hodges和Greg Hannon博士。戚益軍博士為本文的通訊作者,。此項(xiàng)研究為科技部863項(xiàng)目和北京市科委資助課題,，在北京生命科學(xué)研究所完成。
生物谷推薦原始出處：
cell on line
Sorting of Small RNAs into Arabidopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide
Shijun Mi,1,3 Tao Cai,1,3 Yugang Hu,1 Yemiao Chen,1 Emily Hodges,2 Fangrui Ni,1 Liang Wu,1 Shan Li,1 Huanyu Zhou,1 Chengzu Long,1 She Chen,1 Gregory J. Hannon,2 and Yijun Qi1,
1 National Institute of Biological Sciences, No.7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
2 Cold Spring Harbor Laboratory, Watson School of Biological Sciences, and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
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.
