Molecular Biology

Trapped in an Eddy Upstream

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Science  18 Jul 2008:
Vol. 321, Issue 5887, pp. 318
DOI: 10.1126/science.321.5887.318b

Almost all eukaryotic genes initiate the translation of their messenger RNA (mRNA) into protein at an AUG start codon (which codes for the amino acid methionine). Ribosomes, the protein-synthesizing engines of the cell, scan from the 5′ end of an mRNA until they find the first AUG, and then start translation. Some mRNAs contain a supernumerary AUG (and associated short coding region) upstream and independent of the main AUG/coding region, and such upstream open reading frames (uORFs) have the potential to regulate the translation of the downstream gene.

Ivanov et al. have found a series of conserved short uORFs associated with genes involved in polyamine synthesis, with the curious feature that they often start with a noncanonical AUU codon and hence have been overlooked in bioinformatic scans. The presence of AUU seems to be critical for the uORF to direct polyamine-directed repression of the downstream coding region; polyamines (such as spermidine) reduce the fidelity of the translation initiation complex for AUG, thus allowing increased production of the AUU uORF at the expense of the downstream polyamine biosynthesis gene—creating an autoregulatory feedback loop. The patchy distribution of these AUU uORFs across the eukaryotic phylogenetic tree suggests that they may have arisen independently on several occasions. — GR

Proc. Natl. Acad. Sci. U.S.A. 105, 10.1073/pnas.0801590105 (2008).

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