分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-12
摘要: Tristetraprolin (TTP) regulates the expression of AU-rich element-containing mRNAs through promoting the degradation and repressing the translation of target mRNA. While the mechanism for promoting target mRNA degradation has been extensively studied, the mechanism underlying translational repression is not well established. Here, we show that TTP recruits eukaryotic initiation factor 4E2 (eIF4E2) to repress target mRNA translation. TTP interacted with eIF4E2 but not with eIF4E. Overexpression of eIF4E2 enhanced TTP-mediated translational repression, and downregulation of endogenous eIF4E2 or overexpression of a truncation mutant of eIF4E2 impaired TTP-mediated translational repression. Overexpression of an eIF4E2 mutant that lost the cap-binding activity also impaired TTP's activity, suggesting that the cap-binding activity of eIF4E2 is important in TTP-mediated translational repression. We further show that TTP promoted eIF4E2 binding to target mRNA. These results imply that TTP recruits eIF4E2 to compete with eIF4E to repress the translation of target mRNA. This notion is supported by the finding that downregulation of endogenous eIF4E2 increased the production of tumor necrosis factor alpha (TNF-alpha) protein without affecting the mRNA levels in THP-1 cells. Collectively, these results uncover a novel mechanism by which TTP represses target mRNA translation.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: The correct ratio of the HIV-1 structural protein Gag to the envelope protein (Env) is important for maximal virion infectivity. How the virus ensures the production of Gag and Env proteins in an appropriate ratio remains unknown. We report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative expression of Gag and Env for efficient production of infectious virions. RVB2 inhibits Gag expression by interacting with both the encoded Matrix (MA) domain of Gag protein and 5' UTR of the translating mRNA and promoting mRNA degradation in a translation-dependent manner. This inhibitory activity of RVB2 is antagonized by Env through competitive interaction with MA, allowing Gag synthesis to proceed when Env levels are adequate for virion assembly. In HIV-1-positive patients, RVB2 levels positively correlate with viral loads and disease progression status. These findings reveal a mechanism by which HIV-1 regulates its protein expression.