TRANSLATIONAL INHIBITION MEDIATED BY A SHORT UPSTREAM OPEN READING FRAME IN THE HUMAN CYTOMEGALOVIRUS GPUL4 (GP48) TRANSCRIPT
TRANSLATIONAL INHIBITION MEDIATED BY A SHORT UPSTREAM OPEN READING FRAME IN THE HUMAN CYTOMEGALOVIRUS GPUL4 (GP48) TRANSCRIPT
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DOI：
10.1128/jvi.67.9.5514-5521.1993
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发表时间：
1993-09-01
影响因子：
5.4
通讯作者：
GEBALLE, AP
中科院分区：
文献类型：
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作者：
DEGNIN, CR;SCHLEISS, MR;GEBALLE, AP
人类巨细胞病毒(CMV)病毒颗粒糖蛋白gpULA(Gp48)基因表达一个转录本，该转录本包含三个AUG密码子，位于启动gp48蛋白合成的密码子的上游。此前，我们报道了这些Aug密码子中的第二个，Aug2，对于抑制下游翻译是必要的，但还不够(M.Schleiss，C.R.Degnin，和A.P.Geballe，J.Virol)。65：6782-6789,1991)。我们现在证明了由Aug2(UORF2)启动的上游开放阅读框架(UORF2)的编码信息对于抑制信号是至关重要的。几个错义突变，特别是涉及uORF2羧基末端密码子的错义突变，使抑制信号失活，而保留uORF2编码内容的突变则统一保留抑制信号。UORF2终止密码子对抑制是必不可少的，但下游更远的前导序列并不关键。在CMV临床分离株中uORF2的保守性表明，uORF2在CMV感染循环中起着重要作用。虽然这些结果表明uORF2的多肽产物介导了抑制作用，但我们证明uORF2信号只在顺式反应中起作用，并提出了gp48 uORF2信号的抑制模型。
The human cytomegalovirus (CMV) virion glycoprotein gpULA (gp48) gene expresses a transcript that contains three AUG codons upstream from the one used to initiate synthesis of the gp48 protein. Previously we reported that the second of these AUG codons, AUG2, was necessary but insufficient for inhibition of downstream translation (M. Schleiss, C. R. Degnin, and A. P. Geballe, J. Virol. 65:6782-6789, 1991). We now demonstrate that the coding information of the upstream open reading frame initiated by AUG2 (uORF2) is critical for the inhibitory signal. Several missense mutations, particularly those involving the carboxy-terminal codons of uORF2, inactivate the inhibitory signal, while mutations that preserve the coding content of uORF2 uniformly retain the inhibitory signal. The uORF2 termination codon is essential for inhibition, but leader sequences further downstream are not critical. Conservation of uORF2 among clinical strains of CMV suggests that uORF2 provides an important function in the CMV infectious cycle. Although these results indicate that the peptide product of uORF2 mediates the inhibitory effect, we demonstrate that the uORF2 signal acts only in cis, and we propose a model of inhibition by the gp48 uORF2 signal.