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

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 prepare from liver, a specific RNA-protein complex (p65) formed. Competition experiments showed that a pyrimidine-rich sequence in the codin region of albumin mRNA was required for the formation of p65. The level of p65 was increased in the RSW extracts prepared from liver c galactosamine-treated rats infused with a standard amino acid formula, compared with a BCAA-enriched amino acid formula. The protein i p65 appears to be polypyrimidine tract-binding protein (PTB), because the formation of p65 was reduced in the RSW extracts pre-incubate with anti-PTB antibody. In cell-free translation analysis, immunodepletion of PTB from rabbit reticulocyte lysate caused an increase albumin translation. These results suggest that binding of PTB to albumin mRNA suppresses its translation. A supply of BCAA may interfe. with this binding and improve the translation efficiency of albumin mRNA in injured liver. (C) 2004 Elsevier B.V. All rights reserved.