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Repression of interrupted and intact rDNA by the SUMO pathway in Drosophila melanogaster

Luo, Yicheng and Fefelova, Elena and Ninova, Maria and Chen, Yung-Chia Ariel and Aravin, Alexei A. (2020) Repression of interrupted and intact rDNA by the SUMO pathway in Drosophila melanogaster. eLife . ISSN 2050-084X. (In Press)

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Ribosomal RNAs (rRNAs) are essential components of the ribosome and are among the most abundant macromolecules in the cell. To ensure high rRNA level, eukaryotic genomes contain dozens to hundreds of rDNA genes, however, only a fraction of the rRNA genes seems to be active, while others are transcriptionally silent. We found that individual rDNA genes have high level of cell-to-cell heterogeneity in their expression in Drosophila melanogaster. Insertion of heterologous sequences into rDNA leads to repression associated with reduced expression in individual cells and decreased number of cells expressing rDNA with insertions. We found that SUMO (Small Ubiquitin-like Modifier) and SUMO ligase Ubc9 are required for efficient repression of interrupted rDNA units and variable expression of intact rDNA. Disruption of the SUMO pathway abolishes discrimination of interrupted and intact rDNAs and removes cell-to-cell heterogeneity leading to uniformly high expression of individual rDNA in single cells. Our results suggest that the SUMO pathway is responsible for both repression of interrupted units and control of intact rDNA expression.

Item Type:Article
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URLURL TypeDescription Paper
Luo, Yicheng0000-0003-3704-2389
Ninova, Maria0000-0001-5051-5502
Aravin, Alexei A.0000-0002-6956-8257
Additional Information:© 2020 eLife Sciences Publications Ltd. Subject to a Creative Commons Attribution license. We thank Katalin Fejes Toth and members of the Aravin lab for discussion and comments. We appreciate the help of Maayan Schwarzkopf and Niles Pierce with HCR FISH experiments. We thank Lynn Yi for help with bioinformatics analysis. We are grateful to Michael Buszczak and the Bloomington Stock Center for providing fly stocks, Igor Dawid for providing rDNA unit constructs. We thank Igor Antoshechkin (Caltech) for help with sequencing. M.N. is supported by NIH/NICHD grant (K99HD099316). This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to A.A.A. Data availability: Sequencing data have been deposited in GEO under accession codes GSE141068 and GSE115277. Other data generated or analysed during this study are included in the manuscript and supporting files.
Funding AgencyGrant Number
NIHR01 GM097363
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20200715-153524216
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104392
Deposited By: Tony Diaz
Deposited On:15 Jul 2020 22:50
Last Modified:16 Nov 2020 22:12

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