Sequence-mediated regulation of adenovirus gene expression by repression of mRNA accumulation.
Sequence-mediated regulation of adenovirus gene expression by repression of mRNA accumulation.
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通过抑制 mRNA 积累来序列介导的腺病毒基因表达调控。
DOI：
10.1128/mcb.17.4.2207
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发表时间：
1997
影响因子：
5.3
通讯作者：
Falck-Pedersen,E
中科院分区：
文献类型：
--
作者：
Prescott,JC;Liu,L;Falck-Pedersen,E
复杂转录单位中的基因表达几乎可以在成熟细胞质mRNA产生的每一步进行调节，包括转录起始、延伸、终止、前mRNA加工、核-细胞质mRNA转运和mRNA稳定性的改变。我们一直在腺病毒主要晚期转录单位（MLTU）中表征多聚腺苷酸位点的替代使用，作为前体mRNA 3′端加工水平调控的模型。MLTU含有5个多聚腺苷酸化位点（L1至L5）。启动子近端位点（L1）在腺病毒感染的早期阶段和当报告质粒的3′端存在多个poly（A）位点时的质粒转染中作为优势poly（A）位点起作用。相反，在病毒DNA复制开始后，在腺病毒感染的晚期发现在所有五个poly（A）位点加工的稳定mRNA。尽管L1在早期感染中占优势，但它在体内和体外都是3′端RNA加工的相对较差的底物。在这项研究中，我们已经调查了早期L1优势的基础。我们发现，含有未加工的L1 poly（A）位点的mRNA进入稳定mRNA稳态库的能力受到损害。这种抑制作用影响前体mRNA的核稳定性或核质转运，需要位于L1 poly（A）位点上游的酸作用序列。
Gene expression in complex transcription units can be regulated at virtually every step in the production of mature cytoplasmic mRNA, including transcription initiation, elongation, termination, pre-mRNA processing, nucleus-to-cytoplasm mRNA transport, and alterations in mRNA stability. We have been characterizing alternative poly(A) site usage in the adenovirus major late transcription unit (MLTU) as a model for regulation at the level of pre-mRNA 3′-end processing. The MLTU contains five polyadenylation sites (L1 through L5). The promoter proximal site (L1) functions as the dominant poly(A) site during the early stage of adenovirus infection and in plasmid transfections when multiple poly(A) sites are present at the 3′ end of a reporter plasmid. In contrast, stable mRNA processed at all five poly(A) sites is found during the late stage of adenovirus infection, after viral DNA replication has begun. Despite its dominance during early infection, L1 is a comparatively poor substrate for 3′-end RNA processing both in vivo and in vitro. In this study we have investigated the basis for the early L1 dominance. We have found that mRNA containing an unprocessed L1 poly(A) site is compromised in its ability to enter the steady-state pool of stable mRNA. This inhibition, which affects either the nuclear stability or nucleus-to-cytoplasm transport of the pre-mRNA, requires acis-acting sequence located upstream of the L1 poly(A) site.