2008年3月13日，北京生命科学研究所戚益军博士实验室在Cell杂志以Immediate Early Publication形式在线发表题为“Sorting of Small RNAs into Arabidopsis Argonaute Complexes is Directed by the 5’ Terminal Nucleotide”的文章 (www.cell.com)。该文报道了在模式植物拟南芥中,小分子RNA 5’末端核苷酸对其进入不同的Argonaute蛋白复合体起到决定作用。
RNA干扰（RNAi）是一种在真核生物中保守的基因表达调控机制。RNAi的效应复合体的核心是一种能结合小分子RNA的Argonaute蛋白。拟南芥拥有10个Argonaute蛋白和大量不同类型的小分子RNAs。这些小分子RNAs进入Argonaute蛋白复合体是否具有选择性和这种选择性由什么因子决定尚不为人所知。戚益军实验室纯化了四个Argonaute蛋白复合物，并对各复合物中的小分子RNA组分进行了大规模序列分析。分析表明不同Argonaute结合的小分子RNAs具有不同的5’末端核苷酸偏好性，比如AGO1结合以U起始的小分子RNAs，而AGO2主要结合以A起始的小分子RNAs。进一步的体外和体内实验证实不同的Argonaute对5’末端核苷酸不同的小分子RNAs的结合活性存在很大差异。改变小分子RNA的5’末端核苷酸可以使小分子RNA进入错误的Argonaute蛋白，并改变其生物学功能。戚益军博士实验室的这一发现表明，小分子RNA的序列本身决定了小分子RNA的最终进入哪个Argonaute蛋白并行使其功能。同时该发现也意味着Argonaute蛋白结合小分子RNA的结构域的进化参与了它们功能的特异化，也为植物microRNAs 5’末端为尿嘧啶的进化动力提供了解释。
密士军博士和蔡涛博士是该文章的共同第一作者，论文的其他作者还有胡玉刚，陈叶苗，倪方锐，武亮，李姗，龙承祖，陈涉和冷泉港实验室的Emily Hodges和Greg Hannon博士。戚益军博士为本文的通讯作者。此项研究为科技部863项目和北京市科委资助课题，在北京生命科学研究所完成。
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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.
