Turnover of aberrant pre-40S pre-ribosomal particles is initiated by a novel endonucleolytic decay pathway.
Turnover of aberrant pre-40S pre-ribosomal particles is initiated by a novel endonucleolytic decay pathway.
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DOI：
10.1093/nar/gky116
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发表时间：
2018-05-18
影响因子：
14.9
通讯作者：
Dez C
中科院分区：
文献类型：
--
作者：
Choque E;Schneider C;Gadal O;Dez C
核糖体生物合成需要200多个反式作用因子来实现两个成熟核糖体亚基的正确产生。在这里，我们已经确定Efg 1作为一种新的，核仁核糖体生物合成因子在酿酒酵母，是直接关联到前40 S颗粒的监督。Efg 1的缺失会损害早期的前rRNA加工，导致18 S rRNA和40 S亚基水平的强烈下降以及异常23 S rRNA的积累。以Efg 1为诱饵，我们揭示了一种新的23 SrRNA降解途径。免疫共沉淀实验表明Efg 1是90 S前体核糖体的组成部分，与35 S前体rRNA和U3 snoRNA结合，但对23 S前体rRNA及其新型降解中间体11 S rRNA具有更强的亲和力。23 S在18 S序列内的新位点Q1处被内切核酸酶Utp 24切割，产生11 S和17 S ' rRNA。这两种切割产物都被TRAMP/外泌体复合物靶向降解。因此，Q1位点定义了一个新的核糖体RNA的内切核酸裂解位点，专门用于监视前核糖体颗粒。
Ribosome biogenesis requires more than 200 trans-acting factors to achieve the correct production of the two mature ribosomal subunits. Here, we have identified Efg1 as a novel, nucleolar ribosome biogenesis factor in Saccharomyces cerevisiae that is directly linked to the surveillance of pre-40S particles. Depletion of Efg1 impairs early pre-rRNA processing, leading to a strong decrease in 18S rRNA and 40S subunit levels and an accumulation of the aberrant 23S rRNA. Using Efg1 as bait, we revealed a novel degradation pathway of the 23S rRNA. Co-immunoprecipitation experiments showed that Efg1 is a component of 90S pre-ribosomes, as it is associated with the 35S pre-rRNA and U3 snoRNA, but has stronger affinity for 23S pre-rRNA and its novel degradation intermediate 11S rRNA. 23S is cleaved at a new site, Q1, within the 18S sequence by the endonuclease Utp24, generating 11S and 17S' rRNA. Both of these cleavage products are targeted for degradation by the TRAMP/exosome complexes. Therefore, the Q1 site defines a novel endonucleolytic cleavage site of ribosomal RNA exclusively dedicated to surveillance of pre-ribosomal particles.
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