RGD Reference Report - A positive feedback regulation of Heme oxygenase 1 by CELF1 in cardiac myoblast cells. - Rat Genome Database

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A positive feedback regulation of Heme oxygenase 1 by CELF1 in cardiac myoblast cells.

Authors: Liu, Yang  Wang, Huiwen  Wang, Jun  Wei, Bin  Zhang, Xinyi  Zhang, Mengqi  Cao, Dong  Dai, Jiang  Wang, Zhen  Nyirimigabo, Eric  Ji, Guangju 
Citation: Liu Y, etal., Biochim Biophys Acta Gene Regul Mech. 2019 Feb;1862(2):209-218. doi: 10.1016/j.bbagrm.2018.11.006. Epub 2018 Nov 30.
RGD ID: 38501076
Pubmed: PMID:30508596   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbagrm.2018.11.006   (Journal Full-text)

As an RNA binding protein, CUG-BP Elav-like family (CELF) has been shown to be critical for heart biological functions. However, no reports have revealed the function of CELF1 in hypertrophic cardiomyopathy (HCM). Hinted by RNA immunoprecipitation-sequencing (RIP-seq) data, the influence of the CELF protein on heme oxygenase-1 (HO-1) expression was tested by modulating CELF1 levels. Cardiac hypertrophy is related to oxidative stress-induced damage. Hence, the cardiovascular system may be protected against further injury by upregulating the expression of antioxidant enzymes, such as HO-1. During the past two decades, research has demonstrated the central role of HO-1 in the protection against diseases. Thus, understanding the molecular mechanisms underlying the modulation of HO-1 expression is profoundly important for developing new strategies to prevent cardiac hypertrophy. To elucidate the molecular mechanisms underlying HO-1 regulation by the CELF protein, we performed RNA immunoprecipitation (RIP), biotin pull-down analysis, luciferase reporter and mRNA stability assays. We found that the expression of HO-1 was downregulated by CELF1 through the conserved GU-rich elements (GREs) in HO-1 3'UTR transcripts. Correspondingly, CELF1 expression was regulated by controlling the release of carbon monoxide (CO) in H9C2 cells. The CELF1-HO-1-CO regulation axis constituted a novel positive feedback circuit. In addition, we detected the potential involvement of CELF1 and HO-1 in samples from HCM patients. We found that CELF1 and CELF2, but not HO-1, were highly expressed in HCM heart samples. Thus, a manipulation targeting CELF1 could be developed as a potential therapeutic option for cardiac hypertrophy.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mRNA destabilization involved_inIDA 38501076PMID:30508596ARUK-UCL 
post-transcriptional gene silencing involved_inIMP 38501076; 38501076PMID:30508596ARUK-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
mRNA 3'-UTR binding enablesIDA 38501076; 38501076PMID:30508596ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Celf1  (CUGBP, Elav-like family member 1)
Celf2  (CUGBP, Elav-like family member 2)


Additional Information