Nature2014-06-24 4:38 PM

Argonaute 在细菌中起防止DNA入侵的作用 DNA-guided DNA interference by a prokaryotic Argonaute

论文摘要 

RNA 干涉 (RNAi) 在真核细胞中的一个功能是,通过一个过程来保护细胞不受外来“小单链RNA” (ssRNAs) 的影响;在这个过程中,被主体编码的短RNA结合同源RNA目标,并介导它们的降解。Argonaute (Ago) 是真核细胞中由RNA引导的RNAi通道的一个关键酶;很多原核生物也具有编码Ago的基因,但它们的生理作用此前仍不清楚。现在,John van der Oost及同事发现,原核生物的Ago (来自细菌Thermus thermophilus) 保护细胞不受DNA而不是RNA入侵。在本例中,Ago被加载了小干涉RNA (与来自质体DNA的小干涉RNA相似),后者结合和劈开互补的DNA。

Abstract 

RNA interference is widely distributed in eukaryotes and has a variety of functions, including antiviral defence and gene regulation1, 2. All RNA interference pathways use small single-stranded RNA (ssRNA) molecules that guide proteins of the Argonaute (Ago) family to complementary ssRNA targets: RNA-guided RNA interference1, 2. The role of prokaryotic Ago variants has remained elusive, although bioinformatics analysis has suggested their involvement in host defence3. Here we demonstrate that Ago of the bacterium Thermus thermophilus (TtAgo) acts as a barrier for the uptake and propagation of foreign DNA. In vivo, TtAgo is loaded with 5′-phosphorylated DNA guides, 13–25 nucleotides in length, that are mostly plasmid derived and have a strong bias for a 5′-end deoxycytidine. These small interfering DNAs guide TtAgo to cleave complementary DNA strands. Hence, despite structural homology to its eukaryotic counterparts, TtAgo functions in host defence by DNA-guided DNA interference.

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