Deletion of drosophila nopp140 induces subcellular ribosomopathies
Abstract
The nucleolar and Cajal body phosphoprotein of 140 kDa (Nopp140) is considered a ribosome assembly factor, but its precise functions remain unknown. To approach this problem, we deleted the Nopp140 gene in Drosophila using FLP-FRT recombination. Genomic PCR, reverse transcriptase-PCR (RT-PCR), and immunofluorescence microscopy confirmed the loss of Nopp140, its messenger RNA (mRNA), and protein products from all tissues examined. Nopp140-/- larvae arrested in the second instar stage and most died within 8 days. While nucleoli appeared intact in Nopp140-/- cells, the C/D small nucleolar ribonucleoprotein (snoRNP) methyltransferase, fibrillarin, redistributed to the nucleoplasm in variable amounts depending on the cell type; RT-PCRs showed that 2'-O-methylation of ribosomal RNA (rRNA) in Nopp140-/- cells was reduced at select sites within both the 18S and 28S rRNAs. Ultrastructural analysis showed that Nopp140-/- cells were deficient in cytoplasmic ribosomes, but instead contained abnormal electron-dense cytoplasmic granules. Immunoblot analysis showed a loss of RpL34, and metabolic labeling showed a significant drop in protein translation, supporting the loss of functional ribosomes. Northern blots showed that pre-RNA cleavage pathways were generally unaffected by the loss of Nopp140, but that R2 retrotransposons that naturally reside within the 28S region of normally silent heterochromatic Drosophila ribosomal DNA (rDNA) genes were selectively expressed in Nopp140-/- larvae.…
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R2 elements displayed preferential induction upon Nopp140 loss as compared to R1 elements.
“Similarly to the effects of the SL1-like impairment, R2 elements displayed preferential induction upon Nopp140 loss as compared to R1 elements (64).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [64]
Loss of a ribosome assembly factor Nopp140 leads to both reduced rRNA synthesis and R2 activation.
“Our assumptions are consistent with previous finding that loss of a ribosome assembly factor Nopp140 leads to both reduced rRNA synthesis (101) and R2 activation (64).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [64]
Cites
Ye, J., & Eickbush, T. H. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01409-06 · Cited by 51 · see citing works
Guerrero, P. A., & Maggert, K. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016401 · Cited by 51 · see citing works
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Fefelova, E. A., Pleshakova, I. M., Mikhaleva, E. A., Pirogov, S. A., Poltorachenko, V. A., Abramov, Y. A., Romashin, D. D., Shatskikh, A. S., Blokh, R. S., Gvozdev, V. A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1276 · Cited by 15 · see citing works
“Our assumptions are consistent with previous finding that loss of a ribosome assembly factor Nopp140 leads to both reduced rRNA synthesis (101) and R2 activation (64).”
BackgroundResultRaje, H. S., Lieux, M. E., & DiMario, P. J. (2018) · Transcription · doi:10.1080/21541264.2018.1506682 · Cited by 13 · see citing works
Self-citationThe retrotransposon <i>R2</i> maintains <i>Drosophila</i> ribosomal DNA repeats
Nelson, J. O., Slicko, A., & Yamashita, Y. M. (2021) · doi:10.1101/2021.07.12.451825 · Cited by 7 · see citing works
- Authors
- He, F., James, A., Raje, H., Ghaffari, H., & DiMario, P.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- DiMario, Patrick
- Venue
- Chromosoma
- Published
- 2014-11-11
- Volume
- 124
- Issue
- 2
- Pages
- 191-208
- ISSN
- 0009-5915 (ISSN-L)
- 1432-0886
- OpenAlex
- W2027977110
- Cited by
- 27
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Chromosoma (publishedVersion)
- PubMed (publishedVersion)
- Civil War Book Review (submittedVersion)
- Funders
- National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- Nopp140, ribosomopathies, ribosome assembly, Drosophila, fibrillarin, nucleolus, R2 retrotransposon, mRNA translation, cytoplasmic ribosomes, developmental lethality
- MeSH terms
- Animals, Cell Nucleus, Chromatin, Chromosomal Proteins, Non-Histone, Drosophila, Female, Male, Nuclear Proteins, Phosphoproteins, Ribosomes, RNA, Ribosomal, Polymerase Chain Reaction, RNA-Binding Proteins, Gene Deletion, Coiled Bodies, Ribonucleoproteins, Small Nucleolar, Genomics, Drosophila Proteins
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