RRC ID |
45608
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著者 |
Nishino T, Matsunaga R, Jikihara H, Uchida M, Maeda A, Qi G, Abe T, Kiyonari H, Tashiro S, Inagaki-Ohara K, Shimamoto F, Konishi H.
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タイトル |
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.
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ジャーナル |
Biochim Biophys Acta
|
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.
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巻・号 |
1861(11)
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ページ |
1816-1827
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公開日 |
2016-11-1
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DOI |
10.1016/j.bbalip.2016.09.006
|
PII |
S1388-1981(16)30243-8
|
PMID |
27616329
|
MeSH |
3' Untranslated Regions / genetics
AU Rich Elements / genetics*
Aging / genetics*
Animals
Base Sequence
COS Cells
Chlorocebus aethiops
ELAV Proteins / metabolism*
Gene Deletion
Gene Expression Regulation
Leptin / genetics*
Leptin / metabolism
Lipid-Linked Proteins / genetics
Lipid-Linked Proteins / metabolism*
Male
Metabolome
Mice, Knockout
Obesity / genetics*
RNA Processing, Post-Transcriptional / genetics
RNA Stability / genetics*
RNA, Messenger / genetics
Sex-Determining Region Y Protein / genetics
Sex-Determining Region Y Protein / metabolism
Subcellular Fractions / metabolism
Transcription, Genetic
|
IF |
3.411
|
引用数 |
1
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
BIOPHYSICS
CELL BIOLOGY
|
リソース情報 |
遺伝子材料 |
pCMFlag_hsGATA1 (RDB06753) |