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The pair of arginine codons AGA AGG close to the initiation codon of the lambda int gene inhibits cell growth and protein synthesis by accumulating peptidyl-tRNAArg4.
Olivares-Trejo, José J; Bueno-Martínez, José G; Guarneros, Gabriel; Hernández-Sánchez, Javier.
Afiliação
  • Olivares-Trejo JJ; Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico.
Mol Microbiol ; 49(4): 1043-9, 2003 Aug.
Article em En | MEDLINE | ID: mdl-12890027
To analyse the mechanism by which rare codons near the initiation codon inhibit cell growth and protein synthesis, we used the bacteriophage lambda int gene or early codon substitution derivatives. The lambda int gene has a high frequency of rare ATA, AGA and AGG codons; two of them (AGA AGG) located at positions 3 and 4 of the int open reading frame (ORF). Escherichia coli pth (rap) cells, which are defective in peptidyl-tRNA hydrolase (Pth) activity, are more susceptible to the inhibitory effects of int expression as compared with wild-type cells. Cell growth and Int protein synthesis were enhanced by overexpression of Pth and tRNAArg4 cognate to AGG and AGA but not of tRNAIle2a specific for ATA. The increase of Int protein synthesis also takes place when the rare arginine codons AGA and AGG at positions 3 and 4 are changed to common arginine CGT or lysine AAA codons but not to rare isoleucine ATA codons. In addition, overexpression of int in Pth defective cells provokes accumulation of peptidyl-tRNAArg4 in the soluble fraction. Therefore, cell growth and Int synthesis inhibition may be due to ribosome stalling and premature release of peptidyl-tRNAArg4 from the ribosome at the rare arginine codons of the first tandem, which leads to cell starvation for the specific tRNA.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Biossíntese de Proteínas / Códon / RNA de Transferência de Arginina / Divisão Celular / Bacteriófago lambda / Códon de Iniciação Idioma: En Revista: Mol Microbiol Assunto da revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Ano de publicação: 2003 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Biossíntese de Proteínas / Códon / RNA de Transferência de Arginina / Divisão Celular / Bacteriófago lambda / Códon de Iniciação Idioma: En Revista: Mol Microbiol Assunto da revista: BIOLOGIA MOLECULAR / MICROBIOLOGIA Ano de publicação: 2003 Tipo de documento: Article País de afiliação: México País de publicação: Reino Unido