DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation
DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation
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DOI：
10.1073/pnas.1106245108
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发表时间：
2011-07-19
影响因子：
11.1
通讯作者：
Kai, Toshie
中科院分区：
文献类型：
--
作者：
Pek, Jun Wei;Kai, Toshie
在有丝分裂过程中，由凝聚蛋白I和凝聚蛋白II复合物介导的染色体分离实现了遗传物质的忠实遗传。染色体分离失败可导致肿瘤形成、不育和出生缺陷。最近，研究证实，种系特异性DEAD-box RNA解旋酶Vasa通过促进凝聚蛋白I组分Barr的染色体定位，促进果蝇有丝分裂染色体分离。这种Vasa的有丝分裂功能是由茄子素和纺锤体e介导的，它们是piwi相互作用RNA途径的两个种系成分。在生殖细胞和体细胞中，染色体的忠实分离都应执行。然而，在体细胞中是否也有类似的促进染色体分离的机制尚未阐明。在这里，我们提出证据，belle （vasa paralog）和RNA干扰途径调节染色体分离在果蝇体细胞。在有丝分裂过程中，belle促进Barr染色体定位和染色体分离。Belle对凝聚染色体的定位依赖于dicer-2和argonaute2。共免疫沉淀实验表明，Belle与Barr和Argonaute2相互作用，并在内源性siRNA（内siRNA）产生位点富集。我们的研究结果表明，Belle通过内切sirna途径促进果蝇体细胞的染色体分离。DDX3（人类belle同源物）和DICER在HeLa细胞中促进染色体分离和hCAP-H（人类Barr同源物）定位，表明这些蛋白在人类细胞中具有保守功能。我们的研究结果表明，RNA解旋酶Belle/DDX3和RNA干扰通路在调节果蝇和人类体细胞的染色体分离中发挥着共同的作用。
During mitosis, faithful inheritance of genetic material is achieved by chromosome segregation, as mediated by the condensin I and II complexes. Failed chromosome segregation can result in neoplasm formation, infertility, and birth defects. Recently, the germ-line-specific DEAD-box RNA helicase Vasa was demonstrated to promote mitotic chromosome segregation in Drosophila by facilitating robust chromosomal localization of Barren (Barr), a condensin I component. This mitotic function of Vasa is mediated by Aubergine and Spindle-E, which are two germ-line components of the Piwi-interacting RNA pathway. Faithful segregation of chromosomes should be executed both in germ-line and somatic cells. However, whether a similar mechanism also functions in promoting chromosome segregation in somatic cells has not been elucidated. Here, we present evidence that belle (vasa paralog) and the RNA interference pathway regulate chromosome segregation in Drosophila somatic cells. During mitosis, belle promotes robust Barr chromosomal localization and chromosome segregation. Belle's localization to condensing chromosomes depends on dicer-2 and argonaute2. Coimmunoprecipitation experiments indicated that Belle interacts with Barr and Argonaute2 and is enriched at endogenous siRNA (endo-siRNA)-generating loci. Our results suggest that Belle functions in promoting chromosome segregation in Drosophila somatic cells via the endo-siRNA pathway. DDX3 (human homolog of belle) and DICER function in promoting chromosome segregation and hCAP-H (human homolog of Barr) localization in HeLa cells, indicating a conserved function for those proteins in human cells. Our results suggest that the RNA helicase Belle/DDX3 and the RNA interference pathway perform a common role in regulating chromosome segregation in Drosophila and human somatic cells.