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Antagonizing effect of CLPABP on the function of HuR as a regulator of ARE-containing leptin mRNA stability and the effect of its depletion on obesity in old male mouse
- Source :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1861:1816-1827
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Cardiolipin and phosphatidic acid-binding protein (CLPABP) is a pleckstrin homology domain-containing protein and is localized on the surface of mitochondria of cultured cells as a large protein–RNA complex. To analyze the physiological functions of CLPABP, we established and characterized a CLPABP knockout (KO) mouse. Although expression levels of CLPABP transcripts in the developmental organs were high, CLPABP KO mice were normal at birth and grew normally when young. However, old male mice presented a fatty phenotype, similar to that seen in metabolic syndrome, in parallel with elevated male- and age-dependent CLPABP gene expression. One of the reasons for this obesity in CLPABP KO mice is dependence on increases in leptin concentration in plasma. The leptin transcripts were also upregulated in the adipose tissue of KO mice compared with wild-type (WT) mice. To understand the difference in levels of the transcriptional product, we focused on the effect of CLPABP on the stability of mRNA involving an AU-rich element (ARE) in its 3′UTR dependence on the RNA stabilizer, human antigen R (HuR), which is one of the CLPABP-binding proteins. Increase in stability of ARE-containing mRNAs of leptin by HuR was antagonized by the expression of CLPABP in cultured cells. Depletion of CLPABP disturbed the normal subcellular localization of HuR to stress granules, and overexpression of CLPABP induced instability of leptin mRNA by inhibiting HuR function. Consequently, leptin levels in old male mice might be regulated by CLPABP expression, which might lead to body weight control.
- Subjects :
- Leptin
Male
0301 basic medicine
Aging
medicine.medical_specialty
Transcription, Genetic
RNA Stability
Adipose tissue
Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Stress granule
Downregulation and upregulation
Internal medicine
Chlorocebus aethiops
Gene expression
medicine
Cardiolipin
Animals
Obesity
RNA, Messenger
RNA Processing, Post-Transcriptional
3' Untranslated Regions
Molecular Biology
Lipid-Linked Proteins
AU Rich Elements
Mice, Knockout
Messenger RNA
Base Sequence
Cell Biology
Sex-Determining Region Y Protein
030104 developmental biology
Endocrinology
ELAV Proteins
Gene Expression Regulation
chemistry
COS Cells
Knockout mouse
Metabolome
Gene Deletion
030217 neurology & neurosurgery
Subcellular Fractions
Subjects
Details
- ISSN :
- 13881981
- Volume :
- 1861
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Accession number :
- edsair.doi.dedup.....2a91f119cb5e1de8071e3da11674ac9e