The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2
| العنوان: | The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2 |
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| المؤلفون: | Markku Varjosalo, Anna Middleton, Shintaro Katayama, Tiina Skoog, Outi Mäkitie, Tiina Öhman, Arne Lindqvist, Elisabet Einarsdottir, Panu E. Kovanen, Juha Kere, Kaarel Krjutškov, Minna Pekkinen, Svetlana Vakkilainen |
| المساهمون: | HUS Children and Adolescents, Children's Hospital, University of Helsinki, Research Programme of Molecular Medicine, Päivi Marjaana Saavalainen / Principal Investigator, Research Programs Unit, Clinicum, Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, Medicum, HUSLAB, Molecular Systems Biology, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Lastentautien yksikkö |
| المصدر: | Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, lcsh:Medicine, Apoptosis, Transcriptome, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, T-LYMPHOCYTES, MOLECULAR-BASIS, Lymphocytes, lcsh:Science, Multidisciplinary, INCREASED APOPTOSIS, Disease genetics, 1184 Genetics, developmental biology, physiology, Cell cycle, Long non-coding RNA, Up-Regulation, 3. Good health, Cell biology, 030220 oncology & carcinogenesis, CARTILAGE-HAIR HYPOPLASIA, RNA, Long Noncoding, LYMPHOCYTE DYSFUNCTION, Signal Transduction, Adult, G2 Phase, EXPRESSION, Cell physiology, Primary Immunodeficiency Diseases, Down-Regulation, Biology, Osteochondrodysplasias, Article, 03 medical and health sciences, Immunological deficiency syndromes, Downregulation and upregulation, Endoribonucleases, REVEALS, Cartilage–hair hypoplasia, medicine, Humans, Hirschsprung Disease, TRANSCRIPTOME, Gene, MUTATIONS, lcsh:R, Immunologic Deficiency Syndromes, RNA, Fibroblasts, medicine.disease, 030104 developmental biology, DEFECT, lcsh:Q, Hair |
| الوصف: | RMRP was the first non-coding nuclear RNA gene implicated in a disease. Its mutations cause cartilage-hair hypoplasia (CHH), an autosomal recessive skeletal dysplasia with growth failure, immunodeficiency, and a high risk for malignancies. This study aimed to gain further insight into the role of RNA Component of Mitochondrial RNA Processing Endoribonuclease (RMRP) in cellular physiology and disease pathogenesis. We combined transcriptome analysis with single-cell analysis using fibroblasts from CHH patients and healthy controls. To directly assess cell cycle progression, we followed CHH fibroblasts by pulse-labeling and time-lapse microscopy. Transcriptome analysis identified 35 significantly upregulated and 130 downregulated genes in CHH fibroblasts. The downregulated genes were significantly connected to the cell cycle. Multiple other pathways, involving regulation of apoptosis, bone and cartilage formation, and lymphocyte function, were also affected, as well as PI3K-Akt signaling. Cell-cycle studies indicated that the CHH cells were delayed specifically in the passage from G2 phase to mitosis. Our findings expand the mechanistic understanding of CHH, indicate possible pathways for therapeutic intervention and add to the limited understanding of the functions of RMRP. |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3074e9dc32b7df77ad9db5a038f13e8Test https://doi.org/10.1038/s41598-019-50334-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e3074e9dc32b7df77ad9db5a038f13e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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