 The study examined the effects of upstream open reading frames, UORFs, on gene expression in yeast cells. It found that while nearly all August-initiated UORFs were strong represses, most non-org UORFs had only weak effects on expression. The study also identified features associated with translational repression and nonsense-mediated decay, NMD, such as UORF sequences and positions within transcript leaders. Furthermore, it suggested that the location of UORFs in transcript leaders was nearly as predictive as UORF sequences. This study provides insight into the scope of natural UORF activity, identifies features associated with translational repression and NMD, and suggests that the locations of UORFs in transcript leaders are nearly as predictive as UORF sequences. This article was authored by Gemma E. May, Christina Akitova, Matthew A. Garjonsen, and others.