Initiation

Figure 17.4. Schematic representation of the mechanism of the ORF sequence-dependent inhibition of initiation, as exemplified by the case of the regulation of S-adenosylmethionine decarboxylase (AdoMetDC) mRNA translation. Translation of the upstream ORF results in the synthesis of the hexapeptide MetAlaGlyAspIleSer (MAGDIS) that seemingly remains bound to the ribosome and somehow blocks termination and further movement along mRNA (upper). Under some conditions, e.g., upon growth stimulation, the scanning ribosomes ignore the ORF initiation signal, scan the mRNA further and initiate at the start of the AdoMetDC coding sequence (lower). (J.R. Hill & D.R. Morris, J. Biol. Chem. 268, 726-731, 1993; H. Ruan, J.R. Hill, S. Fatemie-Nainie & D.R. Morris, J. Biol. Chem. 269, 17905-17910, 1994).

Figure 17.4. Schematic representation of the mechanism of the ORF sequence-dependent inhibition of initiation, as exemplified by the case of the regulation of S-adenosylmethionine decarboxylase (AdoMetDC) mRNA translation. Translation of the upstream ORF results in the synthesis of the hexapeptide MetAlaGlyAspIleSer (MAGDIS) that seemingly remains bound to the ribosome and somehow blocks termination and further movement along mRNA (upper). Under some conditions, e.g., upon growth stimulation, the scanning ribosomes ignore the ORF initiation signal, scan the mRNA further and initiate at the start of the AdoMetDC coding sequence (lower). (J.R. Hill & D.R. Morris, J. Biol. Chem. 268, 726-731, 1993; H. Ruan, J.R. Hill, S. Fatemie-Nainie & D.R. Morris, J. Biol. Chem. 269, 17905-17910, 1994).

mechanism of this regulation is obscure. Either a reduced initiation at the ORF initiation codon or a decreased interaction of the peptide with the ribosome may be responsible for the effect of arginine depletion.

17.4.2. ORF-Mediated Regulation of Yeast Transcription Factor GCN4

Translational regulation of the synthesis of a yeast transcription factor, called GCN4, is a different and more complicated case (for reviews, see Hinnebusch & Klausner, 1991; Hinnebusch et al., 1993; Hinnebusch, 1996). The GCN4 mRNA contains four very short upstream open reading frames (ORFs) in its long leader sequence, located between 150 and 360 nucleotides upstream of the initiation codon (Fig. 17.5). The di- and tri-peptide sequences synthesised on the ORFs are hardly of a decisive importance for

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