Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes
Autor: | Kristiina Tammimies, Esko Kankuri, Mari H. Tervaniemi, Juha Kere, Kristo Nuutila, Shintaro Katayama, H. Annika Siitonen, Jyrki Vuola, Outi Elomaa, Tiina Skoog, Sari Suomela |
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Přispěvatelé: | Research Programs Unit, University of Helsinki, Department of Medical and Clinical Genetics, Medicum, Research Programme for Molecular Neurology, Plastiikkakirurgian yksikkö, Clinicum, Department of Pharmacology, Department of Dermatology, Allergology and Venereology, Esko Markus Kankuri / Principal Investigator, Juha Kere / Principal Investigator, Research Programme of Molecular Medicine, HUS Musculoskeletal and Plastic Surgery |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Intracellular Space P-body NORMALIZATION 0302 clinical medicine Cytoskeleton Skin Regulation of gene expression MESSENGER-RNA DECAY 318 Medical biotechnology Intracellular Signaling Peptides and Proteins 1184 Genetics developmental biology physiology HCR ASSOCIATION RNAseq mRNA surveillance Cell biology PROBE LEVEL 030220 oncology & carcinogenesis PSORS1 Research Article Signal Transduction Biotechnology Gene isoform lcsh:QH426-470 lcsh:Biotechnology FIBRONECTIN Biology Adherens junction 03 medical and health sciences lcsh:TP248.13-248.65 P-bodies Genetics Humans Psoriasis PSORS1 LOCUS Expression profiling Centrosome VULGARIS HEK 293 cells KERATINOCYTES COMPONENTS Cell adhesion CCHCR1 Gene expression profiling lcsh:Genetics HEK293 Cells 030104 developmental biology Gene Expression Regulation Haplotypes 3121 General medicine internal medicine and other clinical medicine 3111 Biomedicine |
Zdroj: | BMC Genomics BMC Genomics, Vol 19, Iss 1, Pp 1-15 (2018) |
Popis: | Background CCHCR1 (Coiled-Coil α-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centrosomal protein, as well as a component of cytoplasmic processing bodies (P-bodies) that regulate mRNA turnover. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings; it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC) haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants. Results The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though several similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies. Conclusions CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and -division. The present findings may explain the previous inconsistent observations about the functions of CCHCR1. Electronic supplementary material The online version of this article (10.1186/s12864-018-4810-y) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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