Format

Send to

Choose Destination
Sci Rep. 2019 Sep 24;9(1):13758. doi: 10.1038/s41598-019-50334-6.

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

Author information

1
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. svetlana.vakkilainen@helsinki.fi.
2
Folkhälsan Research Center, Institute of Genetics, Helsinki, Finland. svetlana.vakkilainen@helsinki.fi.
3
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
4
Folkhälsan Research Center, Institute of Genetics, Helsinki, Finland.
5
Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland.
6
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
7
Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
8
Institute of Biotechnology, and Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
9
Competence Centre on Health Technologies, Tartu, Estonia.
10
Department of Pathology, University of Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki, Finland.
11
Department of Medical and Molecular Genetics, King's College, London, UK.
12
Department of Molecular Medicine and Surgery, Karolinska Institutet and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.

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.

PMID:
31551465
DOI:
10.1038/s41598-019-50334-6
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center