Cells alter their t RAN abundance to selectively regulate protein synthesis during stress conditions (Sci Signal. 2018, 11(546): pii:eaat6409)

報告日期: 2019/04/12
報告時間: 17:10/18:00
報告學生: 劉詩凱
講評老師: 劉宗霖
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Cells Alter Their tRNA Abundance to Selectively Regulate Protein Synthesis During Stress Conditions

Sci Signal. 2018 Sep 4;11(546)

Speaker: Shi-Kai Liu                         

Coordinator: Chien-hung Yu                    Date/Time: 2019/04/12 17:10-18:00

Commentator: Tsung-lin Liu, Ph.D.                     Location: Room 602

The information on the mRNA must be converted into the amino acid sequence of the protein through tRNA. It is generally accepted that the imbalance between the codon usage and cognate tRNAs may have implications for cellular homeostasis, quality control of protein biogenesis, and disease. It has been shown that yeast stress-responsive genes are unexpectedly enriched in codons that use rare tRNAs. In this study, the authors wondered whether cells selectively regulate protein synthesis during stress conditions by altering tRNA abundance. They measured relative tRNA abundance profiles under four stress conditions (oxidative stress, osmotic stress, temperature stress, and diauxic shift) and the results showed that tRNA abundances changed substantially in a reproducible manner. By using t-distributed stochastic neighborhood embedding (t-SNE) and K-means clustering, they divided T into three clusters and found that each cluster had its unique functional characteristics. These observations suggest that tRNA pools are rearranged under stress conditions and influence translation efficiency. In order to understand the codon usage of yeast genes was adapted to the tRNA abundance under normal and stress conditions. The authors calculated the tRNA adaptive index under normal conditions (n-tAI) and stress conditions (s-tAI). The results showed that the genes related to external stimulus responses had better codon adaptation under stress conditions. To study the changes of s-tAI whether affect the rate of protein production. They designed monomeric enhanced green fluorescent protein (mEGFP) variants with identical amino acid sequence but different codon usage, and observed that the translation efficiency of a given transcript may change significantly when the tRNA pool is altered during stress. Additionally, the authors used a stochastic model observed that the genes that up-regulated during the environmental stress response showed a higher s-tAI and increased protein production rate. And they also performed a bayesian statistics to build a model that explains the changes in protein abundance are highly dependent on changes in tRNA abundance, which significant modifications on protein production rates. In conclusion, the authors suggest that the adaptability of codons to tRNA pools is an independent mechanism that fine-tunes protein abundance and complements other mechanisms, such as transcriptional regulation, transcriptional degradation, and initiation of translation.

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