Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast
Inhibition of splicing and nuclear retention of pre-mRNA by spliceostatin A in fission yeast
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DOI：
10.1016/j.bbrc.2007.10.029
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发表时间：
2007-12-21
影响因子：
3.1
通讯作者：
Yoshida, Minoru
中科院分区：
文献类型：
--
作者：
Lo, Chor-Wai;Kaida, Daisuke;Yoshida, Minoru
前mrna的核保留受到几种安全机制的严格调控，这些机制阻止前mrna输出到细胞质中。最近，一种有效的抗肿瘤微生物代谢物FR901464的甲基化衍生物spliceostatin A被发现在哺乳动物细胞中引起pre-mRNA的积累和翻译。在这里，我们报道剪接抑素A也抑制剪接和前mrna的核保留在一个裂变酵母菌株缺乏多药耐药蛋白Pmd1。在哺乳动物细胞中观察到，剪接抑素A与剪接体中SF3b复合物的组分结合。此外，酿酒酵母MLP1的同源物nup211的过表达会抑制spliceostatin a积累的pre-mRNA的翻译。这些结果表明SF3b复合物在pre-mRNA保留中具有保守作用，这与MLP1的功能无关。(C) 2007爱思唯尔公司版权所有。
Nuclear retention of pre-mRNAs is tightly regulated by several security mechanisms that prevent pre-mRNA export into the cytoplasm. Recently, spliceostatin A, a methylated derivative of a potent antitumor microbial metabolite FR901464, was found to cause pre-mRNA accumulation and translation in mammalian cells. Here we report that spliceostatin A also inhibits splicing and nuclear retention of pre-mRNA in a fission yeast strain that lacks the multidrug resistance protein Pmd1. As observed in mammalian cells, spliceostatin A is bound to components of the SF3b complex in the spliceosome. Furthermore, overexpression of nup211, a homolog of Saccharomyces cerevisiae MLP1, suppresses translation of pre-mRNAs accumulated by spliceostatin A. These results suggest that the SF3b complex has a conserved role in pre-mRNA retention, which is independent of the Mlp1 function. (C) 2007 Elsevier Inc. All rights reserved.