Posttranscriptional regulation of albumin gene expression by branched-chain amino acids in rats with acute liver injury

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2004-12-24 DOI:10.1016/j.bbadis.2004.08.011

Masashi Kuwahata , Yasuko Kuramoto , Yuka Tomoe , Emi Sugata , Hiroko Segawa , Mikiko Ito , Tatsuzo Oka , Ken-ichi Miyamoto

{"title":"Posttranscriptional regulation of albumin gene expression by branched-chain amino acids in rats with acute liver injury","authors":"Masashi Kuwahata , Yasuko Kuramoto , Yuka Tomoe , Emi Sugata , Hiroko Segawa , Mikiko Ito , Tatsuzo Oka , Ken-ichi Miyamoto","doi":"10.1016/j.bbadis.2004.08.011","DOIUrl":null,"url":null,"abstract":"<div><div>We previously demonstrated that the integration of albumin mRNA into functional polysomes was regulated by the supply of branched-chain amino acids (BCAA) in the liver of galactosamine-treated rats. To study the mechanism of this regulation, we investigated interaction between rat liver proteins and albumin transcripts. When albumin transcript was incubated with ribosome salt wash (RSW) extracts prepared from liver, a specific RNA–protein complex (p65) formed. Competition experiments showed that a pyrimidine-rich sequence in the coding region of albumin mRNA was required for the formation of p65. The level of p65 was increased in the RSW extracts prepared from liver of galactosamine-treated rats infused with a standard amino acid formula, compared with a BCAA-enriched amino acid formula. The protein in p65 appears to be polypyrimidine tract-binding protein (PTB), because the formation of p65 was reduced in the RSW extracts pre-incubated with anti-PTB antibody. In cell-free translation analysis, immunodepletion of PTB from rabbit reticulocyte lysate caused an increase in albumin translation. These results suggest that binding of PTB to albumin mRNA suppresses its translation. A supply of BCAA may interfere with this binding and improve the translation efficiency of albumin mRNA in injured liver.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1739 1","pages":"Pages 62-69"},"PeriodicalIF":4.2000,"publicationDate":"2004-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. Molecular basis of disease","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0925443904001553","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

We previously demonstrated that the integration of albumin mRNA into functional polysomes was regulated by the supply of branched-chain amino acids (BCAA) in the liver of galactosamine-treated rats. To study the mechanism of this regulation, we investigated interaction between rat liver proteins and albumin transcripts. When albumin transcript was incubated with ribosome salt wash (RSW) extracts prepared from liver, a specific RNA–protein complex (p65) formed. Competition experiments showed that a pyrimidine-rich sequence in the coding region of albumin mRNA was required for the formation of p65. The level of p65 was increased in the RSW extracts prepared from liver of galactosamine-treated rats infused with a standard amino acid formula, compared with a BCAA-enriched amino acid formula. The protein in p65 appears to be polypyrimidine tract-binding protein (PTB), because the formation of p65 was reduced in the RSW extracts pre-incubated with anti-PTB antibody. In cell-free translation analysis, immunodepletion of PTB from rabbit reticulocyte lysate caused an increase in albumin translation. These results suggest that binding of PTB to albumin mRNA suppresses its translation. A supply of BCAA may interfere with this binding and improve the translation efficiency of albumin mRNA in injured liver.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

支链氨基酸对急性肝损伤大鼠白蛋白基因表达的转录后调控

我们之前已经证明，在半乳糖胺处理的大鼠肝脏中，白蛋白mRNA整合到功能性多体中受到支链氨基酸（BCAA）供应的调节。为了研究这种调节的机制，我们研究了大鼠肝脏蛋白和白蛋白转录物之间的相互作用。当白蛋白转录物与从肝脏制备的核糖体盐洗（RSW）提取物一起孵育时，形成了特定的rna -蛋白复合物（p65）。竞争实验表明，白蛋白mRNA编码区富含嘧啶的序列是p65形成的必要条件。与富含bcaa的氨基酸配方相比，在半乳糖胺处理大鼠肝脏中注入标准氨基酸配方的RSW提取物中，p65的水平升高。p65中的蛋白似乎是多嘧啶束结合蛋白（PTB），因为在抗PTB抗体预孵育的RSW提取物中p65的形成减少。在无细胞翻译分析中，兔网织细胞裂解液中PTB的免疫缺失导致白蛋白翻译增加。这些结果表明PTB与白蛋白mRNA的结合抑制了其翻译。BCAA的供应可能会干扰这种结合，提高损伤肝脏中白蛋白mRNA的翻译效率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.