Liu J M, Green S W, Shimada T, Young N S
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
J Virol. 1992 Aug;66(8):4686-92. doi: 10.1128/JVI.66.8.4686-4692.1992.
Vertebrate parvoviruses share a similar genomic organization, with the capsid proteins encoded by genes on the right side and nonstructural proteins encoded by genes on the left side. The temporal and cell-specific appearances of these two types of gene products are regulated by a variety of genetic mechanisms. Rodent parvovirus structural proteins, for example, are encoded by a separate promoter which is positively regulated by nonstructural-gene products. In contrast, for the human B19 parvovirus, the analogous structural-gene promoter is nonfunctional, and both left- and right-side transcripts originate from a single promoter and are highly processed. Using a combination of sensitive RNA analyses of wild-type and mutant templates, we have found that the relative abundance of these alternatively processed transcripts appears to be governed by unique postinitiation events. In permissive cells, the steady-state level of right-side structural-gene transcripts predominates over that of left-side nonstructural-gene transcripts. In nonpermissive cells transfected with the B19 virus genome, nonstructural-gene transcripts predominate. Removal of 3' processing signals located in the middle of the viral genome increases transcription of the far right side. Disruption of a polyadenylation signal in this region makes readthrough of full-length right-side transcripts possible. These results suggest that the abundance of B19 virus RNAs is determined by active 3' processing and is coupled to DNA template replication.
脊椎动物细小病毒具有相似的基因组结构,衣壳蛋白由右侧基因编码,非结构蛋白由左侧基因编码。这两类基因产物的出现时间和细胞特异性受多种遗传机制调控。例如,啮齿动物细小病毒的结构蛋白由一个单独的启动子编码,该启动子受非结构基因产物的正向调控。相比之下,对于人类B19细小病毒,类似的结构基因启动子无功能,左右两侧的转录本均来自单个启动子并经过高度加工。通过对野生型和突变模板进行灵敏的RNA分析相结合,我们发现这些经过不同加工的转录本的相对丰度似乎受独特的起始后事件控制。在允许性细胞中,右侧结构基因转录本的稳态水平高于左侧非结构基因转录本。在用B19病毒基因组转染的非允许性细胞中,非结构基因转录本占主导。去除位于病毒基因组中间的3'加工信号会增加最右侧的转录。破坏该区域的多聚腺苷酸化信号可使全长右侧转录本通读。这些结果表明,B19病毒RNA的丰度由活跃的3'加工决定,并与DNA模板复制相关。