Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
PLoS One. 2010 Feb 9;5(2):e9114. doi: 10.1371/journal.pone.0009114.
Initiation factor eIF4G is a key regulator of eukaryotic protein synthesis, recognizing proteins bound at both ends of an mRNA to help recruit messages to the small (40S) ribosomal subunit. Notably, the genomes of a wide variety of eukaryotes encode multiple distinct variants of eIF4G. We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions. Not all mRNAs are equally sensitive to loss of eIF4G1; genes that encode messages with longer poly(A) tails are preferentially affected. However, eIF4G1-deletion strains contain significantly lower levels of total eIF4G, relative to eIF4G2-delete or wild type strains. Homogenic strains, which encode two copies of either eIF4G1 or eIF4G2 under native promoter control, express a single isoform at levels similar to the total amount of eIF4G in a wild type cell and have a similar capacity to support normal translation initiation rates. Polysome microarray analysis of these strains and the wild type parent showed that translationally active mRNAs are similar. These results suggest that total eIF4G levels, but not isoform-specific functions, determine mRNA-specific translational efficiency.
起始因子 eIF4G 是真核生物蛋白质合成的关键调节因子，可识别结合在 mRNA 两端的蛋白质，帮助将信息募集到小（40S）核糖体亚基。值得注意的是，多种真核生物的基因组编码多种不同的 eIF4G 变体。我们发现，在标准实验室条件下，缺失 eIF4G1 而非 eIF4G2 会损害芽殖酵母的生长和全局翻译起始速率。并非所有的 mRNA 对 eIF4G1 的缺失都同样敏感；具有更长 poly(A) 尾巴的基因优先受到影响。然而，与 eIF4G2 缺失或野生型菌株相比，eIF4G1 缺失菌株的总 eIF4G 水平显著降低。同源菌株在天然启动子控制下编码两个 eIF4G1 或 eIF4G2 的拷贝，以类似于野生型细胞中 eIF4G 总量的水平表达单一同工型，并且具有支持正常翻译起始速率的相似能力。对这些菌株和野生型亲本的多核糖体微阵列分析表明，翻译活性的 mRNA 相似。这些结果表明，总 eIF4G 水平，而不是同工型特异性功能，决定了 mRNA 的特异性翻译效率。
