Protein kinase A regulates gene-specific translational adaptation in differentiating yeast.
Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here we investigate translational reprogramming in yeast during cellular adaptation to the absence of glucose, a stimulus that induces invasive filamentous differentiation. Using ribosome footprint profiling and RNA sequencing to assay gene-specific translation activity genome-wide, we show that prolonged glucose withdrawal is accompanied by gene-specific changes in translational efficiency that significantly affect expression of the majority of genes. Notably, transcripts from a small minority (<5%) of genes make up the majority of translating mRNA in both rapidly dividing and starved differentiating cells, and the identities of these highly translated messages are almost nonoverlapping between conditions. Furthermore, these two groups of messages are subject to condition-dependent translational privilege. Thus the "housekeeping" process of translation does not stay constant during cellular differentiation but is highly adapted to different growth conditions. By comparing glucose starvation to growth-attenuating stresses that do not induce invasive filamentation, we distinguish a glucose-specific translational response mediated through signaling by protein kinase A (PKA). Together, these findings reveal a high degree of growth-state specialization of the translatome and identify PKA as an important regulator of gene-specific translation activity.
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Pavanapuresan P
PP
Vaidyanathan
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Boris
B
Zinshteyn
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Mary K
MK
Thompson
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Wendy V
WV
Gilbert
D000222:Adaptation, Physiological / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D005947:Glucose / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D015003:Yeasts / Q000235:genetics*
D005656:Fungal Proteins; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose
PKA signaling; adaptation to stress; glucose starvation; translatome specialization; yeast invasive growth