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首页> 外文期刊>Journal of Cellular Physiology >Discovery and characterization of novel trans‐spliced products of human polyoma JC virus late transcripts from PML patients
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Discovery and characterization of novel trans‐spliced products of human polyoma JC virus late transcripts from PML patients

机译:发现和描述的小说人类多瘤JC病毒的反式拼接应承担的产品晚从PML病人记录

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Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a rare fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (~5?kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis ‐splicing. Here, we report the discovery and characterization of two novel open reading frames (ORF1 and ORF2) associated with JCV late transcripts, generated by an unusual splicing process called trans ‐splicing. These ORFs result from (i) the trans ‐splicing of two different lengths of the 5′‐short coding region of VP1 between the coding regions of agnoprotein and VP2 after replacing the intron located between these two coding regions and (ii) frame‐shifts occurring within the VP2 coding sequences terminated by a stop codon. ORF1 and ORF2 are capable of encoding 58 and 72 aa long proteins respectively and are expressed in infected cells and PML patients. Each ORF protein shares a common coding region with VP1 and has a unique coding sequence of their own. When the expression of the unique coding regions of ORFs is blocked by a stop codon insertion in the viral background, the mutant virus replicates less efficiently when compared to wild‐type, suggesting that the newly discovered ORFs play critical roles in the JCV life cycle.
机译:虽然人类的亲神经的多瘤病毒,JC病毒(JCV),是孤立的近半个世纪前,理解的分子机制管理其生物学仍然难以捉摸。感染少突胶质细胞和星形胶质细胞中枢神经系统(CNS)和罕见的原因致命的脑疾病称为进步多病灶的脑白质病(PML)免疫力低下的个人包括艾滋病。有一个小环状DNA基因组(~ 5 ? kb)和生成两个主要从其早期抄本和后期的编码区域,生产一些预测或者拼接产品主要通过cis的拼接。和两个开放阅读小说的特征帧(ORF1和ORF2)与JCV迟了成绩单、生成的一个不寻常的拼接过程被称为反式剪接。(我)两个不同的反式剪接应承担的5 '的长度短的VP1编码区agnoprotein和VP2的编码之间的地区后替换这些之间的基因内区位于两个编码区域,(2)框架的转变发生在VP2编码序列由一个终止密码子结束。编码58和72 aa长蛋白质的能力分别,在感染细胞表达和PML的病人。常见的编码区VP1和有一个独特的自己的编码序列。独特的orf编码区域的屏蔽由一个终止密码子插入在病毒背景下,变异病毒复制少了有效地理野生型相比,表明新发现的orf玩JCV生命周期中的关键角色。

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