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Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon

Fefelova, Elena A. and Pleshakova, Irina M. and Mikhaleva, Elena A. and Pirogov, Sergei A. and Poltorachenko, Valentin A. and Abramov, Yuri A. and Romashin, Daniil D. and Shatskikh, Aleksei S. and Blokh, Roman S. and Gvozdev, Vladimir A. and Klenov, Mikhail S. (2022) Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon. Nucleic Acids Research, 50 (2). pp. 867-884. ISSN 0305-1048. PMCID PMC8789037. doi:10.1093/nar/gkab1276. https://resolver.caltech.edu/CaltechAUTHORS:20220120-890531000

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Abstract

Eukaryotic genomes harbor hundreds of rRNA genes, many of which are transcriptionally silent. However, little is known about selective regulation of individual rDNA units. In Drosophila melanogaster, some rDNA repeats contain insertions of the R2 retrotransposon, which is capable to be transcribed only as part of pre-rRNA molecules. rDNA units with R2 insertions are usually inactivated, although R2 expression may be beneficial in cells with decreased rDNA copy number. Here we found that R2-inserted rDNA units are enriched with HP1a and H3K9me3 repressive mark, whereas disruption of the heterochromatin components slightly affects their silencing in ovarian germ cells. Surprisingly, we observed a dramatic upregulation of R2-inserted rRNA genes in ovaries lacking Udd (Under-developed) or other subunits (TAF1b and TAF1c-like) of the SL1-like complex, which is homologues to mammalian Selective factor 1 (SL1) involved in rDNA transcription initiation. Derepression of rRNA genes with R2 insertions was accompanied by a reduction of H3K9me3 and HP1a enrichment. We suggest that the impairment of the SL1-like complex affects a mechanism of selective activation of intact rDNA units which competes with heterochromatin formation. We also propose that R2 derepression may serve as an adaptive response to compromised rRNA synthesis.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1093/nar/gkab1276DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8789037/PubMed CentralArticle
ORCID:
AuthorORCID
Klenov, Mikhail S.0000-0001-8530-0675
Additional Information:© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Received September 06, 2021; Revised November 21, 2021; Editorial Decision December 09, 2021; Accepted December 14, 2021. We thank Michael Buszczak for udd¹ and udd^(null) fly stocks and Udd antibodies, Robert J. Duronio for fly stocks used for H3K9 histone replacement, Sarah Elgin for HP1a antibodies, Yuri Y. Shevelyov for helpful comments on the manuscript, Sergey A. Lavrov for the help in ChIP preparation, Vladimir E. Alatortsev for the bioinformatic analysis of Udd protein. The work was carried out with the use of the equipment of the common use center «Center of Cell and Gene Technology», Institute of Molecular Genetics of National Research Centre «Kurchatov Institute». We are grateful to the Center for Precision Genome Editing and Genetic Technologies for Biomedicine of the Pirogov Russian National Research Medical University (Moscow) for RNA-seq preparation and the Genomics Core Facility of Skolkovo Institute of Science and Technology (Moscow) for ChIP-seq. The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. FUNDING: Russian Science Foundation (RSF) [19–14-00382 to M.S.K.]. Funding for open access charge: Russian Science Foundation [19–14-00382 to M.S.K.]. Conflict of interest statement. None declared.
Funders:
Funding AgencyGrant Number
Russian Science Foundation19-14-00382
Issue or Number:2
PubMed Central ID:PMC8789037
DOI:10.1093/nar/gkab1276
Record Number:CaltechAUTHORS:20220120-890531000
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220120-890531000
Official Citation:Elena A Fefelova, Irina M Pleshakova, Elena A Mikhaleva, Sergei A Pirogov, Valentin A Poltorachenko, Yuri A Abramov, Daniil D Romashin, Aleksei S Shatskikh, Roman S Blokh, Vladimir A Gvozdev, Mikhail S Klenov, Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon, Nucleic Acids Research, Volume 50, Issue 2, 25 January 2022, Pages 867–884, https://doi.org/10.1093/nar/gkab1276
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113023
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:21 Jan 2022 18:08
Last Modified:01 Feb 2022 18:27

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