The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set
DDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. <i>belle</i>, the single <i>DDX3 </i>ortholog<i> </i>in <i>Drosophila,</i> is required for fly viability, fertility, and germline stem cell ma...
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MDPI AG
2020-02-01
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| author | Alexei A. Kotov Baira K. Godneeva Oxana M. Olenkina Vladimir E. Adashev Mikhail V. Trostnikov Ludmila V. Olenina |
| author_facet | Alexei A. Kotov Baira K. Godneeva Oxana M. Olenkina Vladimir E. Adashev Mikhail V. Trostnikov Ludmila V. Olenina |
| author_sort | Alexei A. Kotov |
| collection | DOAJ |
| description | DDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. <i>belle</i>, the single <i>DDX3 </i>ortholog<i> </i>in <i>Drosophila,</i> is required for fly viability, fertility, and germline stem cell maintenance. Belle is involved both in translational activation and repression of target mRNAs in different tissues; however, direct targets of Belle in the testes are essentially unknown. Here we showed that <i>belle</i> RNAi knockdown in testis cyst cells caused a disruption of adhesion between germ and cyst cells and generation of tumor-like clusters of stem-like germ cells. Ectopic expression of <i>β-integrin</i> in cyst cells rescued early stages of spermatogenesis in <i>belle</i> knockdown<i> </i>testes, indicating that integrin adhesion complexes are required for the interaction between somatic and germ cells in a cyst. To address Belle functions in spermatogenesis in detail we performed cross-linking immunoprecipitation and sequencing (CLIP-seq) analysis and identified multiple mRNAs that interacted with Belle in the testes. The set of Belle targets includes transcripts of proteins that are essential for preventing the tumor-like clusters of germ cells and for sustaining spermatogenesis. By our hypothesis, failures in the translation of a number of mRNA targets additively contribute to developmental defects observed in the testes with<i> belle</i> knockdowns both in cyst cells and in the germline. |
| first_indexed | 2024-03-12T18:23:12Z |
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| language | English |
| last_indexed | 2024-03-12T18:23:12Z |
| publishDate | 2020-02-01 |
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| series | Cells |
| spelling | doaj.art-8242699994464048af341fd1340b73c72023-08-02T08:40:25ZengMDPI AGCells2073-44092020-02-019355010.3390/cells9030550cells9030550The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA SetAlexei A. Kotov0Baira K. Godneeva1Oxana M. Olenkina2Vladimir E. Adashev3Mikhail V. Trostnikov4Ludmila V. Olenina5These authors contributed equally to this work.These authors contributed equally to this work.Institute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Sq., 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Sq., 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Sq., 123182 Moscow, RussiaInstitute of Molecular Genetics, Russian Academy of Sciences, 2 Kurchatov Sq., 123182 Moscow, RussiaDDX3 subfamily DEAD-box RNA helicases are essential developmental regulators of RNA metabolism in eukaryotes. <i>belle</i>, the single <i>DDX3 </i>ortholog<i> </i>in <i>Drosophila,</i> is required for fly viability, fertility, and germline stem cell maintenance. Belle is involved both in translational activation and repression of target mRNAs in different tissues; however, direct targets of Belle in the testes are essentially unknown. Here we showed that <i>belle</i> RNAi knockdown in testis cyst cells caused a disruption of adhesion between germ and cyst cells and generation of tumor-like clusters of stem-like germ cells. Ectopic expression of <i>β-integrin</i> in cyst cells rescued early stages of spermatogenesis in <i>belle</i> knockdown<i> </i>testes, indicating that integrin adhesion complexes are required for the interaction between somatic and germ cells in a cyst. To address Belle functions in spermatogenesis in detail we performed cross-linking immunoprecipitation and sequencing (CLIP-seq) analysis and identified multiple mRNAs that interacted with Belle in the testes. The set of Belle targets includes transcripts of proteins that are essential for preventing the tumor-like clusters of germ cells and for sustaining spermatogenesis. By our hypothesis, failures in the translation of a number of mRNA targets additively contribute to developmental defects observed in the testes with<i> belle</i> knockdowns both in cyst cells and in the germline.https://www.mdpi.com/2073-4409/9/3/550ddx3 rna helicasetumorigenesisdrosophila testesgermline stem cellscyst cellstranslational regulationclip-seq analysis |
| spellingShingle | Alexei A. Kotov Baira K. Godneeva Oxana M. Olenkina Vladimir E. Adashev Mikhail V. Trostnikov Ludmila V. Olenina The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set Cells ddx3 rna helicase tumorigenesis drosophila testes germline stem cells cyst cells translational regulation clip-seq analysis |
| title | The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set |
| title_full | The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set |
| title_fullStr | The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set |
| title_full_unstemmed | The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set |
| title_short | The <i>Drosophila</i> RNA Helicase Belle (DDX3) Non-Autonomously Suppresses Germline Tumorigenesis Via Regulation of a Specific mRNA Set |
| title_sort | i drosophila i rna helicase belle ddx3 non autonomously suppresses germline tumorigenesis via regulation of a specific mrna set |
| topic | ddx3 rna helicase tumorigenesis drosophila testes germline stem cells cyst cells translational regulation clip-seq analysis |
| url | https://www.mdpi.com/2073-4409/9/3/550 |
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