人类T细胞白血病病毒2型Rex蛋白在体外剪接体形成的早期阶段抑制前体mRNA剪接。
Human T-cell leukemia virus type 2 Rex inhibits pre-mRNA splicing in vitro at an early stage of spliceosome formation.
作者信息
Bakker A, Li X, Ruland C T, Stephens D W, Black A C, Rosenblatt J D
机构信息
Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine, California 90024-1678, USA.
出版信息
J Virol. 1996 Aug;70(8):5511-8. doi: 10.1128/JVI.70.8.5511-5518.1996.
Abstract
The Rex protein is an essential regulator of RNA expression in human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) that promotes the accumulation of full-length and partially spliced viral transcripts in the cytoplasm. Rex-mediated regulation correlates with specific binding to a cognate RNA recognition element which overlaps the 5' splice site in the viral long terminal repeat. It has been unclear whether Rex directly affects splicing or only nuclear-to-cytoplasmic transport of viral mRNA. We demonstrate that HTLV-2 Rex is a potent inhibitor of splicing in vitro at an early step in spliceosome assembly. Inhibition requires phosphorylation of Rex and the ability of Rex to bind to the Rex response element. Direct inhibition of early spliceosome assembly by Rex may account for differential accumulation of unspliced transcripts and represents a novel mechanism of retroviral gene regulation.
摘要
雷克斯蛋白是人类1型和2型T细胞白血病病毒（HTLV-1和HTLV-2）中RNA表达的重要调节因子，它能促进全长和部分剪接的病毒转录本在细胞质中积累。雷克斯介导的调节与特异性结合一个同源RNA识别元件相关，该元件与病毒长末端重复序列中的5'剪接位点重叠。目前尚不清楚雷克斯是直接影响剪接，还是仅影响病毒mRNA从细胞核到细胞质的转运。我们证明，HTLV-2雷克斯在体外剪接体组装的早期阶段是一种有效的剪接抑制剂。抑制作用需要雷克斯的磷酸化以及雷克斯与雷克斯反应元件结合的能力。雷克斯对早期剪接体组装的直接抑制作用可能解释了未剪接转录本的差异积累，并代表了一种逆转录病毒基因调节的新机制。
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