Upstream Open Reading Frames as Regulators of mRNA Translation

Continuing discoveries of new and surprising mechanisms of gene regulation suggest that our understanding of this complex and ubiquitous biological process remains incomplete. Emerging examples illustrate that many and perhaps all genes are regulated at multiple steps including transcription, posttranscriptional processing, nuclear export and localization, stability, and translation of mature mRNA molecules. Translation itself is regulated by a diverse collection of mechanisms that act not only at the initiation step but also during elongation and termination and even after termination. Among the various cis elements in mRNAs (43) that participate in regulating translation are AUG codons within transcript leaders (upstream AUGs [uAUGs]) and, in some cases, associated upstream open reading frames (uORFs). Based on a 1987 survey, less than 10 % of eukaryotic mRNAs contain