Codon usage limitation in the expression of HIV-1 envelope glycoprotein
Codon usage limitation in the expression of HIV-1 envelope glycoprotein
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DOI：
10.1016/s0960-9822(02)00482-7
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发表时间：
1996-03-01
期刊：
影响因子：
9.2
通讯作者：
Seed, B
中科院分区：
文献类型：
--
作者：
Haas, J;Park, EC;Seed, B
背景：已知人类免疫缺陷病毒 1 型 (HIV-I) 的 env 和 gag 基因产物的表达均受到病毒 RNA 中的顺式元件的限制，这些元件阻碍从细胞核中流出并降低翻译效率。事实证明，识别这些元件很困难，因为它们似乎在整个病毒基因组中传播。结果：在这里，我们报告选择性密码子使用似乎占了病毒 RNA 中的很大一部分。 病毒蛋白合成效率低下，独立于对改善核输出的任何影响，密码子使用效应并不特定于 HIV-1 起源的转录本。用最流行的 HIV-1 密码子重新设计模型蛋白 (Thy-1) 的编码序列会显着损害 Thy-1 的表达，而改变水母绿色荧光蛋白基因的编码序列以符合高表达的人类蛋白的偏好密码子会导致表达效率大幅提高。结论：密码子使用效应是 HIV-1 有效表达的主要障碍 尽管哺乳动物基因不像大肠杆菌基因那样表现出严重的偏差，但在哺乳动物细胞中表达不良的其他蛋白质可以从密码子重新设计中受益。
Background: The expression of both the env and gag gene products of human immunodeficiency virus type 1 (HIV-I) is known to be limited by cis elements in the viral RNA that impede egress from the nucleus and reduce the efficiency of translation, Identifying these elements has proven difficult, as they appear to be disseminated throughout the viral genome.Results: Here, we report that selective codon usage appears to account for a substantial fraction of the inefficiency of viral protein synthesis, independent of any effect on improved nuclear export, The codon usage effect is not specific to transcripts of HIV-1 origin. Re-engineering the coding sequence of a model protein (Thy-1) with the most prevalent HIV-1 codons significantly impairs Thy-1 expression, whereas altering the coding sequence of the jellyfish green fluorescent protein gene to conform to the favored codons of highly expressed human proteins results in a substantial increase in expression efficiency,Conclusions: Codon-usage effects are a major impediment to the efficient expression of HIV-I genes, Although mammalian genes do not show as profound a bias as do Escherichia coli genes, other proteins that are poorly expressed in mammalian cells can benefit from codon re-engineering.