The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2

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Vakkilainen , S , Skoog , T , Einarsdottir , E , Middleton , A , Pekkinen , M , Öhman , T , Katayama , S , Krjutškov , K , Kovanen , P E , Varjosalo , M , Lindqvist , A , Kere , J & Mäkitie , O 2019 , ' The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2 ' , Scientific Reports , vol. 9 , no. 1 , 13758 . https://doi.org/10.1038/s41598-019-50334-6

Title: The human long non-coding RNA gene RMRP has pleiotropic effects and regulates cell-cycle progression at G2
Author: Vakkilainen, Svetlana; Skoog, Tiina; Einarsdottir, Elisabet; Middleton, Anna; Pekkinen, Minna; Öhman, Tiina; Katayama, Shintaro; Krjutškov, Kaarel; Kovanen, Panu E.; Varjosalo, Markku; Lindqvist, Arne; Kere, Juha; Mäkitie, Outi
Contributor: University of Helsinki, HUS Children and Adolescents
University of Helsinki, Research Programme of Molecular Medicine
University of Helsinki, HUS Children and Adolescents
University of Helsinki, Institute of Biotechnology
University of Helsinki, Medicum
University of Helsinki, Molecular Systems Biology
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, HUS Children and Adolescents
Date: 2019-09-24
Language: eng
Number of pages: 9
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/306670
Abstract: 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.
Subject: 1184 Genetics, developmental biology, physiology
CARTILAGE-HAIR HYPOPLASIA
LYMPHOCYTE DYSFUNCTION
INCREASED APOPTOSIS
MOLECULAR-BASIS
T-LYMPHOCYTES
EXPRESSION
MUTATIONS
TRANSCRIPTOME
REVEALS
DEFECT
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