Protein translation from uORFs: roles in stress

The current view of an mRNA is that of a central coding sequence (CDS) flanked by 5′ and 3′ untranslated regions (UTRs). But often UTRs contain open reading frames which, as revealed by ribosome profiling, can also be translated. The effect of these upstream and downstream ORFs (uORFs and dORFs) on the translation of the CDS, or on the production of micropeptides, is still largely unknown.

We have investigated uORF translation in yeast using ribosome profiling data from three different studies in which oxidative stress or starvation conditions were induced. During stress there is a general arrest of CDS translation. But surprisingly, we observe that uORF translation is much less affected, with the vast majority of genes showing an increase in the uORF to CDS translation ratio. Only in a specific subset of mRNAs this goes in the other direction; such regulatory uORFs decrease their translation during stress, permitting the efficient translation of the downstream CDS. The question remains as to the consequences of the increase translation of uORFs during stress, potentially generating hundreds of yet uncharacterized micropeptides. Are these small proteins of functional significance? And if so, how do they protect the cells from stress? New questions that will stimulate more research.

The article has been published in BMC Molecular Cell Biology:
Simone G. Moro, Cedric Hermans, Jorge Ruiz-Orera, M.Mar Albà. Impact of uORFs in mediating regulation of translation in stress conditions. BMC Mol Cell Biol 22, Article number: 29 (2021).

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