Elimination of 01/A'-A0 pre-rRNA processing by-product in human cells involves cooperative action of two nuclear exosome-associated nucleases: RRP6 and DIS3.
Elimination of 01/A'-A0 pre-rRNA processing by-product in human cells involves cooperative action of two nuclear exosome-associated nucleases: RRP6 and DIS3.
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DOI：
10.1261/rna.066589.118
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Tomecki R
中科院分区：
文献类型：
--
作者：
Kobyłecki K;Drążkowska K;Kuliński TM;Dziembowski A;Tomecki R
前rRNA加工通过多阶段去除周围的5′-ETS/3′-ETS和中间的ITS 1/ITS 2片段产生成熟的18 S、5.8S和28 S/25 S rRNA。核酸内切活性释放需要消除的副产物。在这里，我们研究了外泌体相关的3′-5′外切核酸酶DIS 3和RRP 6在人类细胞中rRNA加工和副产物消除中的相互作用。与以前的报道一致，我们观察到这些酶功能障碍后5.8S和18 S前体的积累。然而，这些表型中没有一个像以前忽视的来自5′-ETS（01/A′-A0）的短RNA物质在非功能性DIS 3细胞中的积累那样明显。我们证明了01/A′-A0的去除不依赖于XRN 2的5′-3′外切核酸水解活性。相反，它在A0裂解后迅速进行，并在几个阶段中仅在3′-5′方向发生-在未知核酸酶的启动下，衰变由RRP 6执行，DIS 3有一定的贡献，而最终阶段主要涉及DIS 3。我们的数据揭示了人类外泌体在5′-ETS去除中的作用。此外，尽管01/A′-A0降解涉及与外泌体环相关的两种核酸酶的作用，类似于5.8S 3′-末端成熟，但很可能与后一过程相反，RRP 6在DIS 3之前或与DIS 3冗余地起作用。
Pre-rRNA processing generates mature 18S, 5.8S, and 28S/25S rRNAs through multistage removal of surrounding 5′-ETS/3′-ETS and intervening ITS1/ITS2 segments. Endonucleolytic activities release by-products, which need to be eliminated. Here, we investigated the interplay of exosome-associated 3′–5′ exonucleases DIS3 and RRP6 in rRNA processing and by-product elimination in human cells. In agreement with previous reports, we observed accumulation of 5.8S and 18S precursors upon dysfunction of these enzymes. However, none of these phenotypes was so pronounced as previously overlooked accumulation of short RNA species derived from 5′-ETS (01/A′–A0), in cells with nonfunctional DIS3. We demonstrate that removal of 01/A′–A0 is independent of the XRN2 5′–3′ exonucleolytic activity. Instead, it proceeds rapidly after A0 cleavage and occurs exclusively in the 3′–5′ direction in several phases—following initiation by an unknown nuclease, the decay is executed by RRP6 with some contribution of DIS3, whereas the ultimate phase involves predominantly DIS3. Our data shed new light onto the role of human exosome in 5′-ETS removal. Furthermore, although 01/A′–A0 degradation involves the action of two nucleases associated with the exosome ring, similarly to 5.8S 3′-end maturation, it is likely that contrary to the latter process, RRP6 acts prior to or redundantly with DIS3.
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影响因子：
14.9
作者：
Drazkowska K;Tomecki R;Stodus K;Kowalska K;Czarnocki-Cieciura M;Dziembowski A
通讯作者：
Dziembowski A
影响因子：
14.9
作者：
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64.8
作者：
Makino, Debora Lika;Baumgaertner, Marc;Conti, Elena
通讯作者：
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