Non3 is an essential Drosophila gene required for proper nucleolus assembly

The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathol...

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Main Authors: E. N. Andreyeva, A. A. Ogienko, A. A. Yushkova, J. V. Popova, G. A. Pavlova, E. N. Kozhevnikova, A. V. Ivankin, M. Gatti, A. V. Pindyurin
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2019-03-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/1935
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author E. N. Andreyeva
A. A. Ogienko
A. A. Yushkova
J. V. Popova
G. A. Pavlova
E. N. Kozhevnikova
A. V. Ivankin
M. Gatti
A. V. Pindyurin
author_facet E. N. Andreyeva
A. A. Ogienko
A. A. Yushkova
J. V. Popova
G. A. Pavlova
E. N. Kozhevnikova
A. V. Ivankin
M. Gatti
A. V. Pindyurin
author_sort E. N. Andreyeva
collection DOAJ
description The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathologies of the nervous system and heart. Here, we report the characterization of the Drosophila Non3 (Novel nucleolar protein 3) gene, which encodes a protein homologous to the human Brix domain-containing Rpf2 that has been shown to control ribosomal RNA (rRNA) processing. We used imprecise P-element excision to generate four new mutant alleles in the Non3 gene. Complementation and phenotypic analyses showed that these Non3 mutations can be arranged in an allelic series that includes both viable and lethal alleles. The strongest lethal allele (Non3∆600) is a genetically null allele that carries a large deletion of the gene and exhibits early lethality when homozygous. Flies heterozygous for Non3∆600 occasionally exhibit a mild reduction in the bristle size, but develop normally and are fertile. However, heteroallelic combinations of viable Non3 mutations (Non3197, Non3310 and Non3259) display a Minute-like phenotype, consisting in delayed development and short and thin bristles, suggesting that they are defective in ribosome biogenesis. We also demonstrate that the Non3 protein localizes to the nucleolus of larval brain cells and it is required for proper nucleolar localization of Fibrillarin, a protein important for post-translational modification and processing of rRNAs. In summary, we generated a number of genetic and biochemical tools that were exploited for an initial characterization of Non3, and will be instrumental for future functional studies on this gene and its protein product.
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publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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spelling doaj-art-6a68bd9357b7490188c8deb6fc5206162025-02-01T09:58:07ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592019-03-0123219019810.18699/VJ19.481891Non3 is an essential Drosophila gene required for proper nucleolus assemblyE. N. Andreyeva0A. A. Ogienko1A. A. Yushkova2J. V. Popova3G. A. Pavlova4E. N. Kozhevnikova5A. V. Ivankin6M. Gatti7A. V. Pindyurin8Institute of Molecular and Cellular Biology, SB RAS.Institute of Molecular and Cellular Biology, SB RAS; Novosibirsk State University.Institute of Molecular and Cellular Biology, SB RAS; Novosibirsk State University.Institute of Molecular and Cellular Biology, SB RAS; Institute of Cytology and Genetics, SB RAS.Institute of Molecular and Cellular Biology, SB RAS.Institute of Molecular and Cellular Biology, SB RAS; Institute of Cytology and Genetics, SB RAS.Institute of Molecular and Cellular Biology, SB RAS.Institute of Molecular and Cellular Biology, SB RAS; IBPM CNR and Department of Biology and Biotechnology, Sapienza University of Rome.Institute of Molecular and Cellular Biology, SB RAS; Novosibirsk State University; Institute of Cytology and Genetics, SB RAS.The nucleolus is a dynamic non-membrane-bound nuclear organelle, which plays key roles not only in ribosome biogenesis but also in many other cellular processes. Consistent with its multiple functions, the nucleolus has been implicated in many human diseases, including cancer and degenerative pathologies of the nervous system and heart. Here, we report the characterization of the Drosophila Non3 (Novel nucleolar protein 3) gene, which encodes a protein homologous to the human Brix domain-containing Rpf2 that has been shown to control ribosomal RNA (rRNA) processing. We used imprecise P-element excision to generate four new mutant alleles in the Non3 gene. Complementation and phenotypic analyses showed that these Non3 mutations can be arranged in an allelic series that includes both viable and lethal alleles. The strongest lethal allele (Non3∆600) is a genetically null allele that carries a large deletion of the gene and exhibits early lethality when homozygous. Flies heterozygous for Non3∆600 occasionally exhibit a mild reduction in the bristle size, but develop normally and are fertile. However, heteroallelic combinations of viable Non3 mutations (Non3197, Non3310 and Non3259) display a Minute-like phenotype, consisting in delayed development and short and thin bristles, suggesting that they are defective in ribosome biogenesis. We also demonstrate that the Non3 protein localizes to the nucleolus of larval brain cells and it is required for proper nucleolar localization of Fibrillarin, a protein important for post-translational modification and processing of rRNAs. In summary, we generated a number of genetic and biochemical tools that were exploited for an initial characterization of Non3, and will be instrumental for future functional studies on this gene and its protein product.https://vavilov.elpub.ru/jour/article/view/1935drosophila melanogasternucleolusminute-like phenotypenon3fibrillarinrpf2brix domainribosome biogenesis
spellingShingle E. N. Andreyeva
A. A. Ogienko
A. A. Yushkova
J. V. Popova
G. A. Pavlova
E. N. Kozhevnikova
A. V. Ivankin
M. Gatti
A. V. Pindyurin
Non3 is an essential Drosophila gene required for proper nucleolus assembly
Вавиловский журнал генетики и селекции
drosophila melanogaster
nucleolus
minute-like phenotype
non3
fibrillarin
rpf2
brix domain
ribosome biogenesis
title Non3 is an essential Drosophila gene required for proper nucleolus assembly
title_full Non3 is an essential Drosophila gene required for proper nucleolus assembly
title_fullStr Non3 is an essential Drosophila gene required for proper nucleolus assembly
title_full_unstemmed Non3 is an essential Drosophila gene required for proper nucleolus assembly
title_short Non3 is an essential Drosophila gene required for proper nucleolus assembly
title_sort non3 is an essential drosophila gene required for proper nucleolus assembly
topic drosophila melanogaster
nucleolus
minute-like phenotype
non3
fibrillarin
rpf2
brix domain
ribosome biogenesis
url https://vavilov.elpub.ru/jour/article/view/1935
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