Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast

Transcription and translation are generally thought of as disconnected processes in eukaryotes; however, under starvation conditions in yeast, the promoter sequence influences not only messenger RNA levels but also several processes downstream of transcription, including the localization of mRNA within the cytoplasm and the translation rate of mRNA. Transcription and translation are generally thought of as disconnected processes in eukaryotes. Here, Brian Zid and Erin O'Shea report that in yeast under starvation conditions, promoter sequences influence not only messenger RNA levels but also other processes downstream of transcription — the localization of the mRNA within the cytoplasm and the mRNA translation rate. Such a mechanism may be an adaption to stressful environmental conditions, enabling selective coordination of protein production at times when overall translation is generally reduced. A universal feature of the response to stress and nutrient limitation is transcriptional upregulation of genes that encode proteins important for survival. Under many such conditions, the overall protein synthesis level is reduced, thereby dampening the stress response at the level of protein expression1. For example, during glucose starvation in Saccharomyces cerevisiae (yeast), translation is rapidly repressed, yet the transcription of many stress- and glucose-repressed genes is increased2,3. Here we show, using ribosomal profiling and microscopy, that this transcriptionally upregulated gene set consists of two classes: one class produces messenger RNAs that are translated during glucose starvation and are diffusely localized in the cytoplasm, including many heat-shock protein mRNAs; and the other class produces mRNAs that are not efficiently translated during glucose starvation and are concentrated in foci that co-localize with P bodies and stress granules, a class that is enriched for mRNAs involved in glucose metabolism. Surprisingly, the information specifying the differential localization and protein production of these two classes of mRNA is encoded in the promoter sequence: promoter responsiveness to heat-shock factor 1 (Hsf1) specifies diffuse cytoplasmic localization and higher protein production on glucose starvation. Thus, promoter sequences can influence not only the levels of mRNAs but also the subcellular localization of mRNAs and the efficiency with which they are translated, enabling cells to tailor protein production to the environmental conditions.