Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6
Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6
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DOI：
10.1006/viro.1999.9875
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发表时间：
1999-09-15
期刊：
影响因子：
3.7
通讯作者：
Gompels, UA
中科院分区：
文献类型：
--
作者：
French, C;Menegazzi, P;Gompels, UA
对人类疱疹病毒-6具有特异性和诊断性的基因很少。U83和U22是其中的两个。U22是独一无二的，而U83编码的是与某些细胞趋化因子的远距离相似性。逆转录聚合酶链式反应、cDNA克隆和序列分析表明，在人类疱疹病毒6型感染细胞中，多聚腺苷RNA转录本对应于U83的少量全长和丰富的剪接形式。对于主要的GT-AG或次要的AT-AC内含子，剪接供体和受体位点都不符合共同的序列。然而，在U83转基因细胞系中也可以检测到剪接形式；因此，新的位点被细胞机制所利用。该内含子可能代表了一个新的次要CT-AC剪接类。这种新颖的剪接通过引入一个中央终止密码子来调节基因的表达，该终止密码子取消了趋化素样分子的产生，导致了编码的截短肽。代谢抑制剂的使用和感染时间进程显示这两个RNA转录本的表达具有即刻早期动力学。然而，全长产物后来积累，依赖于病毒DNA复制，类似于U22。对16株菌株的序列分析显示，U83有较高的变异(13%)，并保留了新的剪接位点。具有代表性的变异株具有相似的表达和剪接产物的动力学，(C)1999年学术出版社。
There are few genes that are specific and diagnostic for human herpesvirus-6. U83 and U22 are two of them. U22 is unique, whereas U83 encodes distant similarity with some cellular chemokines. Reverse transcription-polymerase chain reaction, cDNA cloning, and sequence analyses show polyadenylated RNA transcripts corresponding to minor full-length and abundant spliced forms of U83 in human herpesvirus 6-infected cells. The splice donor and acceptor sites do not fit consensus sequences for either major GT-AG or minor AT-AC introns. However, the spliced form can also be detected in a U83 transfected cell line; thus the novel sites are used by cellular mechanisms. This intron may represent a new minor CT-AC splicing class. The novel splicing regulates gene expression by introducing a central stop codon that abrogates production of the chemokine-like molecule, resulting in an encoded truncated peptide. The use of metabolic inhibitors and an infection time course showed expression of the two RNA transcripts with immediate early kinetics. However, the full-length product accumulated later, dependent on virus DNA replication, similar to U22. Sequence analyses of 16 strains showed high variation (13%) in U83,with conservation of the novel splice sites. Representative strain Variants had similar kinetics of expression and spliced products, (C) 1999 Academic Press.