Department of Biological Sciences and Temasek Life Sciences Laboratory, The National University of Singapore, Singapore 117604.
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12007-12. doi: 10.1073/pnas.1106245108. Epub 2011 Jul 5.
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.
在有丝分裂过程中，通过凝聚素 I 和 II 复合物介导的染色体分离来实现遗传物质的忠实遗传。染色体分离失败可能导致肿瘤形成、不孕和出生缺陷。最近，生殖系特异性 DEAD 盒 RNA 解旋酶 Vasa 被证明通过促进 Barren（Barr）的强有力的染色体定位来促进果蝇的有丝分裂染色体分离，Barr 是凝聚素 I 的一个组成部分。Vasa 的这种有丝分裂功能是由 Aubergine 和 Spindle-E 介导的，它们是 Piwi 相互作用 RNA 途径的两个生殖系成分。染色体的正确分离应该在生殖细胞和体细胞中都执行。然而，是否存在类似的机制也可以促进体细胞中的染色体分离尚不清楚。在这里，我们提供的证据表明 belle（vasa 同源物）和 RNA 干扰途径调节果蝇体细胞中的染色体分离。在有丝分裂过程中，belle 促进 Barr 染色体的强大定位和染色体分离。belle 定位于浓缩染色体取决于 dicer-2 和 argonaute2。共免疫沉淀实验表明，Belle 与 Barr 和 Argonaute2 相互作用，并富集在内源性 siRNA（endo-siRNA）产生的基因座上。我们的结果表明，Belle 通过 endo-siRNA 途径在果蝇体细胞中发挥促进染色体分离的作用。DDX3（belle 的人同源物）和 DICER 在促进染色体分离和 hCAP-H（Barr 的人同源物）在 HeLa 细胞中的定位中起作用，表明这些蛋白在人类细胞中具有保守的功能。我们的结果表明，RNA 解旋酶 Belle/DDX3 和 RNA 干扰途径在调节果蝇和人类体细胞中的染色体分离中具有共同作用。
