Upstream open reading frames (uORFs) are known to regulate a few specific transcripts, and recent computational and experimental studies have suggested candidate uORF regulation across the genome. In this issue, Johnstone et al (2016) use ribosome profiling to identify translated uORFs and measure their effects on downstream translation. Furthermore, they show that regulatory uORFs are conserved across species and subject to selective constraint. Recognizing the potential of uORFs in regulating translation expands our understanding of the dynamic regulation of gene expression.
See also: TG Johnstone et al (April 2016)
Differences in the translation level of distinct mRNAs play an important role in controlling the production of the encoded protein. Changes in translation drive posttranscriptional gene expression programs that play critical roles in diverse processes ranging from cellular stress responses to memory formation. Despite the importance of differential translation, we have a limited understanding of the cis‐acting mRNA features that determine the stability or translation state of an mRNA (Brar et al, 2012; Arribere & Gilbert, 2013; Calvo et al, 2009). Johnstone et al (2016) now provide evidence for a global impact of short upstream open reading frames (uORFs) on translation.
In eukaryotes, the small subunit of the ribosome typically scans from the 5′ end of an mRNA until it …
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