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首页> 外文期刊>Molecular and Cellular Biology >Sequence-mediated regulation of adenovirus gene expression by repression of mRNA accumulation.
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Sequence-mediated regulation of adenovirus gene expression by repression of mRNA accumulation.

机译：通过抑制mRNA积累，序列介导的腺病毒基因表达调控。

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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 a cis-acting sequence located upstream of the L1 poly(A) site.
机译：复杂转录单位中的基因表达几乎可以在成熟细胞质mRNA产生的每个步骤中进行调节，包括转录起始，延伸，终止，mRNA加工前处理，细胞核至细胞质mRNA的运输以及mRNA稳定性的改变。我们一直在表征腺病毒主要后期转录单位（MLTU）中的替代poly（A）网站使用情况，作为在mRNA前3'末端加工水平进行调控的模型。 MLTU包含五个聚腺苷酸化位点（L1至L5）。启动子近端位点（L1）在腺病毒感染的早期阶段以及当报告质粒的3'端存在多个poly（A）位点时在质粒转染中充当主要的poly（A）位点。相反，在病毒DNA复制开始后，在腺病毒感染的晚期发现了在所有五个poly（A）位点处加工的稳定mRNA。尽管在早期感染中占主导地位，但L1还是体内和体外3'端RNA处理的相对较差的底物。在这项研究中，我们研究了早期L1优势的基础。我们发现包含未处理的L1 poly（A）位点的mRNA进入稳定mRNA稳态池的能力受到损害。这种抑制作用会影响pre-mRNA的核稳定性或核到细胞质的运输，需要位于L1 poly（A）位点上游的顺式作用序列。

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