RNase III-mediated silencing of a glucose-dependent repressor in yeast
RNase III-mediated silencing of a glucose-dependent repressor in yeast
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DOI：
10.1016/j.cub.2004.12.001
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发表时间：
2005-01-26
期刊：
影响因子：
9.2
通讯作者：
Abou Elela, S
中科院分区：
文献类型：
--
作者：
Ge, DL;Lamontagne, B;Abou Elela, S
RNase III 家族的成员存在于除古细菌之外的所有检查物种中，其中 RNase III 的功能是由凸出螺旋凸出核酸酶 (BHB) 执行的 [1]。在细菌中，RNase III 有助于许多非编码 RNA 的加工，并直接切割多种细胞和噬菌体 mRNA [2, 3]。在真核生物中，RNase III 的直系同源物参与许多 miRNA [19, 20] 和 siRNA [21] 的生物发生，并且这种生物发生启动了几种 mRNA 的降解或翻译抑制 [22-25]。然而，真核 RNase III 通过直接切割 mRNA 编码序列来调节基因表达的能力仍然是推测性的。在这里，我们表明，RNase III 家族的成员 Rnt1p 通过直接切割 mRNA 编码序列内的茎环结构来选择性抑制面包酵母中的基因表达。对 Rnt1p 删除后 mRNA 表达的分析揭示了葡萄糖依赖性阻遏蛋白 Mig2p 的上调。删除 Rnt1p 后，Mig2p mRNA 变得更加稳定，并能抵抗葡萄糖依赖性降解。在体外，Rnt1p 裂解 Mig2p mRNA，而破坏 Rnt1p 信号的沉默突变则阻止了 Mig2p mRNA 的降解。这些观察结果揭示了真核 mRNA 降解的新的 RNase III 依赖性机制。
Members of the RNase III family are found in all species examined with the exception of archaebacteria, where the functions of RNase III are carried out by the bulge-helix-bulge nuclease (BHB) [1]. In bacteria, RNase III contributes to the processing of many noncoding RNAs and directly cleaves several cellular and phage mRNAs [2, 3]. In eukaryotes, orthologs of RNase III participate in the biogenesis of many miRNAs [19, 20] and siRNAs [21], and this biogenesis initiates the degradation or translational repression of several mRNAs [22-25]. However, the capacity of eukaryotic RNase Ills to regulate gene expression by directly cleaving within the coding sequence of mRNAs remains speculative. Here we show that Rnt1p, a member of the RNase III family, selectively inhibits gene expression in baker's yeast by directly cleaving a stem-loop structure within the mRNA coding sequence. Analysis of mRNA expression upon the deletion of Rnt1p revealed an upregulation of the glucose-dependent repressor Mig2p. Mig2p mRNA became more stable upon the deletion of Rnt1p and resisted glucose-dependent degradation. In vitro, Rnt1p cleaved Mig2p mRNA and a silent mutation that disrupts Rnt1p signals blocked Mig2p mRNA degradation. These observations reveal a new RNase III-dependent mechanism of eukaryotic mRNA degradation.