RRC ID 45608
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.
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.
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.
巻・号 1861(11)
ページ 1816-1827
公開日 2016-11-1
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)