The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression.
The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression.
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DOI：
10.1091/mbc.e09-10-0913
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发表时间：
2010-08-15
影响因子：
3.3
通讯作者：
Masuda S
中科院分区：
文献类型：
--
作者：
Yamazaki T;Fujiwara N;Yukinaga H;Ebisuya M;Shiki T;Kurihara T;Kioka N;Kambe T;Nagao M;Nishida E;Masuda S
UAP 56和URH 49，人类中密切相关的RNA解旋酶，分别形成不同的mRNA输出机制，hTREX复合物和AREX复合物。这些解旋酶调节不同的基因组，其中包括有丝分裂因子。与它们的靶基因一致，每个解旋酶是有丝分裂过程中不同步骤所必需的。mRNA的核输出是真核生物基因表达的重要过程。TREX复合物将基因表达从转录和剪接耦合到mRNA输出。Sub 2是酵母中TREX复合物的核心组分，在人类中已经多样化为两种密切相关的RNA解旋酶，UAP 56和URH 49。在这里，我们发现URH 49形成了一种新的URH 49-CIP 29复合物，称为AREX（替代mRNA输出）复合物，而UAP 56形成了人类TREX复合物。由这些解旋酶调节的mRNA在全基因组水平上是不同的。这两组靶mRNA包含关键有丝分裂调节因子的不同子集。与它们的靶mRNA一致，UAP 56的缺失导致有丝分裂延迟和姐妹染色单体凝聚缺陷，而URH 49的缺失导致染色体臂分辨缺陷和胞质分裂失败。此外，其他人TREX组分或CIP 29的消耗导致有丝分裂缺陷，分别类似于在UAP 56或URH 49消耗的细胞中观察到的那些。两者结合起来，这两种密切相关的RNA解旋酶已经进化形成了不同的mRNA输出机制，它们在不同的步骤调节有丝分裂。
UAP56 and URH49, closely related RNA helicases in humans, form different mRNA export machineries, the hTREX complex and the AREX complex, respectively. These helicases regulate different sets of genes, among which are mitotic factors. Consistent with their target genes, each helicase is required for a different step in the mitotic process. Nuclear export of mRNA is an essential process for eukaryotic gene expression. The TREX complex couples gene expression from transcription and splicing to mRNA export. Sub2, a core component of the TREX complex in yeast, has diversified in humans to two closely related RNA helicases, UAP56 and URH49. Here, we show that URH49 forms a novel URH49–CIP29 complex, termed the AREX (alternative mRNA export) complex, whereas UAP56 forms the human TREX complex. The mRNAs regulated by these helicases are different at the genome-wide level. The two sets of target mRNAs contain distinct subsets of key mitotic regulators. Consistent with their target mRNAs, depletion of UAP56 causes mitotic delay and sister chromatid cohesion defects, whereas depletion of URH49 causes chromosome arm resolution defects and failure of cytokinesis. In addition, depletion of the other human TREX components or CIP29 causes mitotic defects similar to those observed in UAP56- or URH49-depleted cells, respectively. Taken together, the two closely related RNA helicases have evolved to form distinct mRNA export machineries, which regulate mitosis at different steps.