title: DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation.
abstract: 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.
authors: Department of Biological Sciences and Temasek Life Sciences Laboratory, The National University of Singapore, Singapore 117604.
authors: Jun Wei
authors: JW
authors: Pek
authors: Toshie
authors: T
authors: Kai
mesh_terms: D000818:Animals; D060565:Argonaute Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins; D047369:Chromatin Immunoprecipitation; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D020365:RNA Helicases / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D034743:RNA-Induced Silencing Complex
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; C103227:Barr protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; C558829:Bel protein, Drosophila; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases