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Calreticulin stabilizes vascular endothelial growth factor‐A mRNA via interaction with AU‐rich element at 3′‐UTR
Author(s) -
Chen ChihYu,
Chien YinChieh,
Lee Hsinyu
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.614.2
Subject(s) - messenger rna , calreticulin , untranslated region , three prime untranslated region , vascular endothelial growth factor , transfection , chemistry , microbiology and biotechnology , rna binding protein , biology , cancer research , endoplasmic reticulum , vegf receptors , gene , biochemistry
Messenger RNA (mRNA) stability is a post‐transcriptional regulation that determines mRNA fate and influences multiple cellular functions. Previous studies have demonstrated that AU‐rich element (ARE) in 3′‐untranslated region (UTR) of mRNA is critical for mRNA stability via interaction with ARE‐binding proteins (ARE‐BPs). Chaperone protein calreticulin (CRT) has been reported to bind the 3′‐UTR, suggesting that it may act as a novel ARE‐BP. The expression level of CRT positively is correlated with the expression of angiogenic factor vascular endothelial growth factor‐A (VEGF‐A). However, the detail regulatory mechanism of CRT on VEGF‐A expression remains elusive. Therefore, we aimed to investigate whether CRT regulates mRNA stability of VEGF‐A through interaction with ARE. Our results showed that depletion of CRT significantly destabilized VEGF‐A mRNA and subsequently decreased the expression levels of both VEGF‐A RNA and protein in PC3 human prostate cancer cell line. Since several AREs were identified in the mRNA of VEGF‐A, we further explore the relationship between CRT and these AREs. Pull‐down analysis demonstrated that CRT directly interacts with the ARE region of VEGF‐A mRNA. In addition, we constructed luciferase vectors contained the ARE of VEGF‐A and co‐transfected with siRNA of CRT or CRT overexpression vector. Our results demonstrated that CRT interacts with ARE in 3′‐UTR of VEGF‐A mRNA. In summary, this study suggests that CRT stabilizes VEGF‐A mRNA through interacting with ARE at the 3′‐UTR of VEGF‐A mRNA. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .