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

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Citações na Scopus
4
Tipo de produção
article
Data de publicação
2020
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Autores
HON, Chung-Chau
ABDULLAH, Aimi Naim
MORETTI, Ana Iochabel S.
POLONI, Joice F.
BONATTO, Diego
HASHIMOTO, Kosuke
CARNINCI, Piero
Citação
BMC GENOMICS, v.21, n.1, article ID 766, 16p, 2020
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
BackgroundProtein 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.ResultsTen 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.ConclusionsOur 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.
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