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
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