LA AUTOANTIGEN ENHANCES AND CORRECTS ABERRANT TRANSLATION OF POLIOVIRUS RNA IN RETICULOCYTE LYSATE

LA AUTOANTIGEN ENHANCES AND CORRECTS ABERRANT TRANSLATION OF POLIOVIRUS RNA IN RETICULOCYTE LYSATE
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DOI:
10.1128/jvi.67.7.3798-3807.1993
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发表时间:
1993-07-01
影响因子:
5.4
通讯作者:
SONENBERG, N
SONENBERG, N
中科院分区:
医学2区
文献类型:
--
作者:
MEEROVITCH, K;SVITKIN, YV;SONENBERG, N

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脊髓灰质炎病毒RNA上的翻译起始通过核糖体与5'非翻译区内的序列的内部结合而发生。我们先前已经描述了一种HeLa细胞蛋白,p52,它与脊髓灰质炎病毒5'非翻译区的一个片段结合(K。Meerovitch,J. Pelletier,and N. Sonenberg,Genes Dev. 3:1026-1034,1989)。在这里,我们报告的HeLa p52的纯化。蛋白质微测序鉴定p52为La自身抗原。La蛋白是一种人类抗原,可被来自自身免疫性疾病(如系统性红斑狼疮和干燥综合征)患者的抗体识别。我们表明,La蛋白刺激脊髓灰质炎病毒RNA的翻译,但不是雀麦花叶病毒,烟草花叶病毒,苜蓿花叶病毒4 RNA,在网织红细胞裂解物中的翻译。此外,La可纠正网织红细胞裂解物中脊髓灰质炎病毒RNA的异常翻译。亚细胞免疫定位显示La蛋白主要分布在细胞核内,但脊髓灰质炎病毒感染后,La蛋白重新分布到细胞质中。我们的研究结果表明,La蛋白参与脊髓灰质炎病毒内部翻译的启动,并可能通过类似的机制在细胞mRNA的翻译功能。
Translation initiation on poliovirus RNA occurs by internal binding of ribosomes to a sequence within the 5' untranslated region. We have previously characterized a HeLa cell protein, p52, that binds to a fragment of the poliovirus 5' untranslated region (K. Meerovitch, J. Pelletier, and N. Sonenberg, Genes Dev. 3:1026-1034, 1989). Here we report the purification of the HeLa p52. Protein microsequencing identified p52 as La autoantigen. The La protein is a human antigen that is recognized by antibodies from patients with autoimmune disorders such as systemic lupus erythematosus and Sjogren's syndrome. We show that the La protein stimulates translation of poliovirus RNA, but not brome mosaic virus, tobacco mosaic virus, and alfalfa mosaic virus 4 RNA, translation in a reticulocyte lysate. In addition, La corrects aberrant translation of poliovirus RNA in a reticulocyte lysate. Subcellular immunolocalization showed that La protein is mainly nuclear, but after poliovirus infection, La is redistributed to the cytoplasm. Our results suggest that La protein is involved in poliovirus internal initiation of translation and might function through a similar mechanism in the translation of cellular mRNAs.