دورية أكاديمية

RNAi-mediated depletion of the NSL complex subunits leads to abnormal chromosome segregation and defective centrosome duplication in Drosophila mitosis.

التفاصيل البيبلوغرافية
العنوان: RNAi-mediated depletion of the NSL complex subunits leads to abnormal chromosome segregation and defective centrosome duplication in Drosophila mitosis.
المؤلفون: Pavlova GA; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia., Popova JV; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Institute of Cytology and Genetics, Siberian Branch of RAS, Novosibirsk, Russia., Andreyeva EN; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia., Yarinich LA; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Lebedev MO; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Razuvaeva AV; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Dubatolova TD; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia., Oshchepkova AL; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of RAS, Novosibirsk, Russia., Pellacani C; IBPM CNR c/o Department of Biology and Biotechnology, Sapienza University of Rome, Rome, Italy., Somma MP; IBPM CNR c/o Department of Biology and Biotechnology, Sapienza University of Rome, Rome, Italy., Pindyurin AV; Institute of Molecular and Cellular Biology, Siberian Branch of RAS, Novosibirsk, Russia.; Novosibirsk State University, Novosibirsk, Russia., Gatti M; IBPM CNR c/o Department of Biology and Biotechnology, Sapienza University of Rome, Rome, Italy.
المصدر: PLoS genetics [PLoS Genet] 2019 Sep 17; Vol. 15 (9), pp. e1008371. Date of Electronic Publication: 2019 Sep 17 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Chromosome Duplication/*genetics , Chromosome Segregation/*genetics , Transcription Factors/*genetics, Animals ; Cell Cycle Proteins/genetics ; Centromere/metabolism ; Centrosome/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Kinetochores/metabolism ; Microtubules/metabolism ; Mitosis/genetics ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Protein Transport/physiology ; RNA Interference ; RNA-Binding Proteins/genetics ; Regulatory Elements, Transcriptional/genetics ; Spindle Apparatus/genetics ; Transcription Factors/metabolism ; Vesicular Transport Proteins/genetics
مستخلص: The Drosophila Nonspecific Lethal (NSL) complex is a major transcriptional regulator of housekeeping genes. It contains at least seven subunits that are conserved in the human KANSL complex: Nsl1/Wah (KANSL1), Dgt1/Nsl2 (KANSL2), Rcd1/Nsl3 (KANSL3), Rcd5 (MCRS1), MBD-R2 (PHF20), Wds (WDR5) and Mof (MOF/KAT8). Previous studies have shown that Dgt1, Rcd1 and Rcd5 are implicated in centrosome maintenance. Here, we analyzed the mitotic phenotypes caused by RNAi-mediated depletion of Rcd1, Rcd5, MBD-R2 or Wds in greater detail. Depletion of any of these proteins in Drosophila S2 cells led to defects in chromosome segregation. Consistent with these findings, Rcd1, Rcd5 and MBD-R2 RNAi cells showed reduced levels of both Cid/CENP-A and the kinetochore component Ndc80. In addition, RNAi against any of the four genes negatively affected centriole duplication. In Wds-depleted cells, the mitotic phenotypes were similar but milder than those observed in Rcd1-, Rcd5- or MBD-R2-deficient cells. RT-qPCR experiments and interrogation of published datasets revealed that transcription of many genes encoding centromere/kinetochore proteins (e.g., cid, Mis12 and Nnf1b), or involved in centriole duplication (e.g., Sas-6, Sas-4 and asl) is substantially reduced in Rcd1, Rcd5 and MBD-R2 RNAi cells, and to a lesser extent in wds RNAi cells. During mitosis, both Rcd1-GFP and Rcd5-GFP accumulate at the centrosomes and the telophase midbody, MBD-R2-GFP is enriched only at the chromosomes, while Wds-GFP accumulates at the centrosomes, the kinetochores, the midbody, and on a specific chromosome region. Collectively, our results suggest that the mitotic phenotypes caused by Rcd1, Rcd5, MBD-R2 or Wds depletion are primarily due to reduced transcription of genes involved in kinetochore assembly and centriole duplication. The differences in the subcellular localizations of the NSL components may reflect direct mitotic functions that are difficult to detect at the phenotypic level, because they are masked by the transcription-dependent deficiency of kinetochore and centriolar proteins.
Competing Interests: The authors have declared that no competing interests exist.
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المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (Drosophila Proteins)
0 (Nuclear Proteins)
0 (RNA-Binding Proteins)
0 (Rcd5 protein, Drosophila)
0 (Transcription Factors)
0 (Vesicular Transport Proteins)
تواريخ الأحداث: Date Created: 20190919 Date Completed: 20200220 Latest Revision: 20200220
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6772098
DOI: 10.1371/journal.pgen.1008371
PMID: 31527906
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7404
DOI:10.1371/journal.pgen.1008371