The Signal Peptide of a Simple Retrovirus Envelope Functions as a Posttranscriptional Regulator of Viral Gene Expression
The Signal Peptide of a Simple Retrovirus Envelope Functions as a Posttranscriptional Regulator of Viral Gene Expression
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DOI：
10.1128/jvi.01833-08
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发表时间：
2009-05-01
影响因子：
5.4
通讯作者：
Palmarini, Massimo
中科院分区：
文献类型：
--
作者：
Caporale, Marco;Arnaud, Frederick;Palmarini, Massimo
逆转录病毒使用不同的策略来调节转录和翻译，并利用参与这些过程的细胞机制。本研究表明，绵羊肺腺瘤病毒（JSRV）包膜糖蛋白（Env）的信号肽在转录后病毒基因表达中起重要作用。JSRV Env的反式表达通过依赖于以下机制的机制增加病毒颗粒产生：（i）其前导序列，（ii）完整的信号肽切割位点，（iii）位于病毒基因组中的顺式作用RNA响应元件，（iv）Crm 1和（v）B23。JSRV Env的信号肽（JSE-SP）长80个氨基酸残基，除了富含精氨酸的RNA结合基序外，还含有推定的核定位和输出信号。JSE-SP定位于内质网和细胞核中，在那里它与核仁标记物共定位。JSE-SP是一种多功能蛋白，因为它适度增强未剪接的病毒mRNA的核输出，并通过促进复制周期的翻译后步骤而显著增加病毒颗粒释放。
Retroviruses use different strategies to regulate transcription and translation and exploit the cellular machinery involved in these processes. This study shows that the signal peptide of the envelope glycoprotein (Env) of Jaagsiekte sheep retrovirus (JSRV) plays a major role in posttranscriptional viral gene expression. Expression of the JSRV Env in trans increases viral particle production by mechanisms dependent on (i) its leader sequence, (ii) an intact signal peptide cleavage site, (iii) a cis-acting RNA-responsive element located in the viral genome, (iv) Crm1, and (v) B23. The signal peptide of the JSRV Env (JSE-SP) is 80 amino acid residues in length and contains putative nuclear localization and export signals, in addition to an arginine-rich RNA binding motif. JSE-SP localizes both in the endoplasmic reticulum and in the nucleus, where it colocalizes with nucleolar markers. JSE-SP is a multifunctional protein, as it moderately enhances nuclear export of unspliced viral mRNA and considerably increases viral particle release by favoring a posttranslational step of the replication cycle.