Protein kinase A regulates gene-specific translational adaptation in differentiating yeast.

Protein kinase A regulates gene-specific translational adaptation in differentiating yeast.
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DOI:
10.1261/rna.044552.114
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发表时间:
2014-06
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Gilbert WV
Gilbert WV
中科院分区:
其他
文献类型:
--
作者:
Vaidyanathan PP;Zinshteyn B;Thompson MK;Gilbert WV

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While translational regulation is widely thought to contribute significantly to cellular differentiation programs, there are few genome-wide studies approaching this question. Here, the authors use ribosome profiling and mRNA-seq to assess gene-specific translation activity genome-wide in response to glucose starvation in yeast. Interestingly, a minority of transcripts comprise the majority of translating mRNA in both rapidly dividing and glucose-starved cells, though the identities of the translationally enriched mRNAs are distinct. Additionally, the authors identify features of the translational response that are specifically mediated by protein kinase A (PKA). These studies nicely reveal growth-state specialization of the “translatome.” 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.
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