Analysis of splice variants of the human protein disulfide isomerase (P4HB) gene.

Autor: Kajihara D; Vascular Biology Laboratory, LIM-64, Heart Institute (InCor), University of Sao Paulo School of Medicine, Av. Eneas Carvalho Aguiar, 44, Annex 2, 9th floor, Sao Paulo, CEP 05403-000, Brazil.; Laboratory for Transcriptome Technology, Division of Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Hon CC; Laboratory for Genome Information Analysis, Division of Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Abdullah AN; Laboratory for Transcriptome Technology, Division of Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Wosniak J Jr; Vascular Biology Laboratory, LIM-64, Heart Institute (InCor), University of Sao Paulo School of Medicine, Av. Eneas Carvalho Aguiar, 44, Annex 2, 9th floor, Sao Paulo, CEP 05403-000, Brazil., Moretti AIS; Vascular Biology Laboratory, LIM-64, Heart Institute (InCor), University of Sao Paulo School of Medicine, Av. Eneas Carvalho Aguiar, 44, Annex 2, 9th floor, Sao Paulo, CEP 05403-000, Brazil., Poloni JF; Department of Molecular Biology and Biotechnology, Biotechnology Center of the Federal University of Rio Grande do Sul, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Bonatto D; Department of Molecular Biology and Biotechnology, Biotechnology Center of the Federal University of Rio Grande do Sul, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Hashimoto K; Laboratory for Transcriptome Technology, Division of Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Laboratory of Computational Biology, Institute for Protein Research, Osaka University, Osaka, 565-0871, Japan., Carninci P; Laboratory for Transcriptome Technology, Division of Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Laurindo FRM; Vascular Biology Laboratory, LIM-64, Heart Institute (InCor), University of Sao Paulo School of Medicine, Av. Eneas Carvalho Aguiar, 44, Annex 2, 9th floor, Sao Paulo, CEP 05403-000, Brazil. francisco.laurindo@incor.usp.br.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2020 Nov 04; Vol. 21 (1), pp. 766. Date of Electronic Publication: 2020 Nov 04.
DOI: 10.1186/s12864-020-07164-y
Abstrakt: Background: Protein Disulfide Isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily with crucial roles in endoplasmic reticulum proteostasis, implicated in many diseases. The family prototype PDIA1 is also involved in vascular redox cell signaling. PDIA1 is coded by the P4HB gene. While forced changes in P4HB gene expression promote physiological effects, little is known about endogenous P4HB gene regulation and, in particular, gene modulation by alternative splicing. This study addressed the P4HB splice variant landscape.
Results: Ten protein coding sequences (Ensembl) of the P4HB gene originating from alternative splicing were characterized. Structural features suggest that except for P4HB-021, other splice variants are unlikely to exert thiol isomerase activity at the endoplasmic reticulum. Extensive analyses using FANTOM5, ENCODE Consortium and GTEx project databases as RNA-seq data sources were performed. These indicated widespread expression but significant variability in the degree of isoform expression among distinct tissues and even among distinct locations of the same cell, e.g., vascular smooth muscle cells from different origins. P4HB-02, P4HB-027 and P4HB-021 were relatively more expressed across each database, the latter particularly in vascular smooth muscle. Expression of such variants was validated by qRT-PCR in some cell types. The most consistently expressed splice variant was P4HB-021 in human mammary artery vascular smooth muscle which, together with canonical P4HB gene, had its expression enhanced by serum starvation.
Conclusions: Our study details the splice variant landscape of the P4HB gene, indicating their potential role to diversify the functional reach of this crucial gene. P4HB-021 splice variant deserves further investigation in vascular smooth muscle cells.
Databáze: MEDLINE
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