Presence of ATG triplets in 5 ' untranslated regions of eukaryotic cDNAs correlates with 'weak' context of the start codon

Motivation: The context of the start codon (typically, AUG) and the feature s of the 5 ' Untranslated Regions (5 ' UTRs) are important for understandin g translation regulation in eukaryotic: mRNAs, and for accurate prediction of the coding! region in genomic and cDNA sequences. The presence of AUG tr iplets in 5 ' UTRs (upstream AUGs) might effect the initiation rate and, in , the context of gene prediction, could! reduce the accuracy of the identif ication of the authentic start. To reveal potential connections between the presence of upstream AUGs and other features of 5 ' UTRs, such as their le ngth and the start codon context, we undertook a systematic analysis of the available eukaryotic 5 ' UTR sequences. Results: We show that a large fraction of 5 ' UTRs in the available cDNA se quences, 15-53% depending on the organism, contain upstream ATGs. A negativ e correlation, was observed between the information content of the translat ion start signal and the length of the 5 ' UTR. Similarly, a negative corre lation exists between the 'strength' of the start context and the number of upstream ATGs. Typically, cDNAs containing long 5 ' UTRs with multiple ups tream AT, Gs have a 'weak' start context, and in contrast, cDNAs, containin g short 5 ' UTRs without ATGs have 'strong' starts. These counter-intuitive results maybe interpreted in terms, of upstream AUGs having an important r ole in the regulation! of translation efficiency by ensuring tow, basal tra nslation level via double negative control and creating the potential for a dditional regulatory mechanisms. One of such mechanisms, supported by exper imental studies of some mRNAs, includes removal of the AUG-containing porti on of the 5 ' UTR by alternative splicing.