title: Posttranscriptional regulation of albumin gene expression by branched-chain amino acids in rats with acute liver injury.
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.
authors.affiliation: Department of Molecular Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan. kuwahata@nutr.med.tokushima-u.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Kuwahata
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kuramoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tomoe
authors.forename: Emi
authors.initials: E
authors.lastname: Sugata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Segawa
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ito
authors.forename: Tatsuzo
authors.initials: T
authors.lastname: Oka
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000418:Albumins / Q000235:genetics* / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002474:Cell-Free System; D015870:Gene Expression; D008099:Liver / Q000293:injuries / Q000502:physiology; D008107:Liver Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D038941:Polypyrimidine Tract-Binding Protein / Q000187:drug effects / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000418:Albumins; D000597:Amino Acids, Branched-Chain; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein