期刊
NUCLEIC ACIDS RESEARCH
卷 47, 期 10, 页码 4974-4985出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz205
关键词
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资金
- Howard Hughes Medical Institute
- National Science Foundation [1650113]
- Moritz-Heyman Discovery Fellowship
- National Institutes of Health [R01GM094314]
- Direct For Education and Human Resources [1650113] Funding Source: National Science Foundation
- Division Of Graduate Education [1650113] Funding Source: National Science Foundation
Regulation of the efficiency with which an mRNA is translated into proteins represents a key mechanism for controlling gene expression. Such regulation impacts the number of actively translating ribosomes per mRNA molecule, referred to as translation efficiency (TE), which can be monitored using ribosome profiling and RNA-seq, or by evaluating the position of an mRNA in a polysome gradient. Here we show that in budding yeast, under nutrient limiting conditions, the commonly used translation inhibitor cycloheximide induces rapid transcriptional upregulation of hundreds of genes involved in ribosome biogenesis. Cycloheximide also prevents translation of these newly transcribed messages, leading to an apparent drop in TE of these genes under conditions that include key transitions during the yeast metabolic cycle, meiosis, and amino acid starvation; however, this effect is abolished when cycloheximide pretreatment is omitted. This response requires TORC1 signaling, and is modulated by the genetic background as well as the vehicle used to deliver the drug. The present work highlights an important caveat to the use of translation inhibitors when measuring TE or mRNA levels, and will hopefully aid in future experimental design as well as interpretation of prior results.
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