VSG mRNA levels are regulated by the production of functional VSG protein.

VSG mRNA levels are regulated by the production of functional VSG protein.
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DOI:
10.1016/j.molbiopara.2020.111348
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发表时间:
2021-01
影响因子:
1.5
通讯作者:
Carrington M
Carrington M
中科院分区:
医学4区
文献类型:
--
作者:
Maudlin IE;Kelly S;Schwede A;Carrington M

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VSG mRNA 拷贝数随 VSG 的身份而变化。过早终止密码子会导致 VSG mRNA 降解。晚期过早终止密码子翻译产生不完整的 VSG,导致 VSG mRNA 增加。非功能性 VSG 产生和 VSG mRNA 水平之间存在反馈途径。布氏锥虫的血流形式通过群体生存策略持续存在于哺乳动物宿主中,该群体生存策略取决于由变体表面糖蛋白(VSG)组成的细胞表面涂层的抗原变异。 VSG 外壳的完整性至关重要,阻断其合成会导致细胞分裂周期在胞质分裂之前停滞。这一观察结果表明 VSG 水平受到监测,并且细胞具有对合成破坏做出反应的机制。在这里,首先通过测量 VSG mRNA 拷贝数,然后使用包含提前终止密码子的 VSG 转基因的异位表达来研究 VSG mRNA 水平的调节。研究结果表明,(i) VSG mRNA 拷贝数随 VSG 的身份而变化,(ii) 一条途径检测到非功能性 VSG 蛋白的合成并导致 VSG mRNA 水平增加。
VSG mRNA copy number varies with the identity of the VSG. Early premature termination codons result in degradation of VSG mRNA. Late premature termination codons translated to produce incomplete VSG result in an increase in VSG mRNA. There is a feedback pathway between non-functional VSG production and VSG mRNA levels. The bloodstream form of Trypanosoma brucei persists in mammalian hosts through a population survival strategy depending on antigenic variation of a cell surface coat composed of the variant surface glycoprotein (VSG). The integrity of the VSG coat is essential and blocking its synthesis results in a cell division cycle arrest just prior to cytokinesis. This observation indicates that VSG levels are monitored and that the cell has mechanisms to respond to a disruption of synthesis. Here, the regulation of VSG mRNA levels has been investigated by first measuring VSG mRNA copy number, and second using ectopic expression of VSG transgenes containing premature termination codons. The findings are that (i) VSG mRNA copy number varies with the identity of the VSG and (ii) a pathway detects synthesis of non-functional VSG protein and results in an increase in VSG mRNA levels.
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