Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis.
Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined the function of Trus during Drosophila development. CRISPR/Cas9...
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Public Library of Science (PLoS)
2025-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011469 |
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| author | Saeko Takada Bonnie J Bolkan MaryJane O'Connor Michael Goldberg Michael B O'Connor |
| author_facet | Saeko Takada Bonnie J Bolkan MaryJane O'Connor Michael Goldberg Michael B O'Connor |
| author_sort | Saeko Takada |
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| description | Toys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined the function of Trus during Drosophila development. CRISPR/Cas9 generated null mutations in trus lead to partial embryonic lethality, significant larval developmental delay, and complete pre-pupal lethality. In mutant larvae, we found decreased cell proliferation and growth defects in the brain and imaginal discs. Mapping relevant tissues for Trus function using trus RNAi and trus mutant rescue experiments revealed that imaginal disc defects are primarily responsible for the developmental delay, while the pre-pupal lethality is likely associated with faulty central nervous system (CNS) development. Examination of the molecular mechanism behind the developmental delay phenotype revealed that trus mutations induce the Xrp1-Dilp8 ribosomal stress-response in growth-impaired imaginal discs, and this signaling pathway attenuates production of the hormone ecdysone in the prothoracic gland. Additional Tap-tagging and mass spectrometry of components in Trus complexes isolated from Drosophila Kc cells identified Ribosomal protein subunit 2 (RpS2), which is coded by string of pearls (sop) in Drosophila, and Eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) as interacting factors. We discuss the implication of these findings with respect to the similarity and differences in trus genetic null mutant phenotypes compared to the haplo-insufficiency phenotypes produced by heterozygosity for mutants in Minute genes and other genes involved in ribosome biogenesis. |
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| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-06-01 |
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| series | PLoS Genetics |
| spelling | doaj-art-a4958cdcdb124e448db431dcdd0b1b2c2025-08-23T05:31:36ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-06-01216e101146910.1371/journal.pgen.1011469Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis.Saeko TakadaBonnie J BolkanMaryJane O'ConnorMichael GoldbergMichael B O'ConnorToys are us (Trus) is the Drosophila melanogaster ortholog of mammalian Programmed Cell Death 2-Like (PDCD2L), a protein that has been implicated in ribosome biogenesis, cell cycle regulation, and oncogenesis. In this study, we examined the function of Trus during Drosophila development. CRISPR/Cas9 generated null mutations in trus lead to partial embryonic lethality, significant larval developmental delay, and complete pre-pupal lethality. In mutant larvae, we found decreased cell proliferation and growth defects in the brain and imaginal discs. Mapping relevant tissues for Trus function using trus RNAi and trus mutant rescue experiments revealed that imaginal disc defects are primarily responsible for the developmental delay, while the pre-pupal lethality is likely associated with faulty central nervous system (CNS) development. Examination of the molecular mechanism behind the developmental delay phenotype revealed that trus mutations induce the Xrp1-Dilp8 ribosomal stress-response in growth-impaired imaginal discs, and this signaling pathway attenuates production of the hormone ecdysone in the prothoracic gland. Additional Tap-tagging and mass spectrometry of components in Trus complexes isolated from Drosophila Kc cells identified Ribosomal protein subunit 2 (RpS2), which is coded by string of pearls (sop) in Drosophila, and Eukaryotic translation elongation factor 1 alpha 1 (eEF1α1) as interacting factors. We discuss the implication of these findings with respect to the similarity and differences in trus genetic null mutant phenotypes compared to the haplo-insufficiency phenotypes produced by heterozygosity for mutants in Minute genes and other genes involved in ribosome biogenesis.https://doi.org/10.1371/journal.pgen.1011469 |
| spellingShingle | Saeko Takada Bonnie J Bolkan MaryJane O'Connor Michael Goldberg Michael B O'Connor Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. PLoS Genetics |
| title | Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. |
| title_full | Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. |
| title_fullStr | Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. |
| title_full_unstemmed | Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. |
| title_short | Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis. |
| title_sort | drosophila trus the orthologue of mammalian pdcd2l is required for proper cell proliferation larval developmental timing and oogenesis |
| url | https://doi.org/10.1371/journal.pgen.1011469 |
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