Department of Biochemistry, Gene Center, University of Munich, 81377 Munich, Germany.
Nat Commun. 2017 May 25;8:15332. doi: 10.1038/ncomms15332.
RNAi is a conserved mechanism in which small RNAs induce silencing of complementary targets. How Argonaute-bound small RNAs are targeted for degradation is not well understood. We show that the adenyl-transferase Cid14, a member of the TRAMP complex, and the uridyl-transferase Cid16 add non-templated nucleotides to Argonaute-bound small RNAs in fission yeast. The tailing of Argonaute-bound small RNAs recruits the 3'-5' exonuclease Rrp6 to degrade small RNAs. Failure in degradation of Argonaute-bound small RNAs results in accumulation of 'noise' small RNAs on Argonaute and targeting of diverse euchromatic genes by RNAi. To protect themselves from uncontrolled RNAi, cid14Δ cells exploit the RNAi machinery and silence genes essential for RNAi itself, which is required for their viability. Our data indicate that surveillance of Argonaute-bound small RNAs by Cid14/Cid16 and the exosome protects the genome from uncontrolled RNAi and reveal a rapid RNAi-based adaptation to stress conditions.
RNAi 是一种保守的机制,其中小 RNA 诱导互补靶标的沉默。Argonaute 结合的小 RNA 如何被靶向降解还不太清楚。我们表明,腺苷转移酶 Cid14(TRAMP 复合物的成员)和尿苷转移酶 Cid16 将非模板核苷酸添加到裂殖酵母中 Argonaute 结合的小 RNA 上。Argonaute 结合的小 RNA 的尾部招募 3'-5' 外切核酸酶 Rrp6 来降解小 RNA。Argonaute 结合的小 RNA 的降解失败会导致“噪音”小 RNA 在 Argonaute 上积累,并通过 RNAi 靶向不同的常染色质基因。为了防止自己受到不受控制的 RNAi 的影响,cid14Δ 细胞利用 RNAi 机制并沉默对 RNAi 本身至关重要的基因,这是它们生存所必需的。我们的数据表明,Cid14/Cid16 和 exosome 对 Argonaute 结合的小 RNA 的监测可以保护基因组免受不受控制的 RNAi 的影响,并揭示了一种基于 RNAi 的快速适应应激条件的机制。