TETHERING RIBOZYMES TO A RETROVIRAL PACKAGING SIGNAL FOR DESTRUCTION OF VIRAL-RNA

TETHERING RIBOZYMES TO A RETROVIRAL PACKAGING SIGNAL FOR DESTRUCTION OF VIRAL-RNA
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DOI:
10.1126/science.8248806
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发表时间:
1993-12-03
期刊:
影响因子:
56.9
通讯作者:
CECH, TR
CECH, TR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SULLENGER, BA;CECH, TR

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RNA 的细胞区室化被认为影响它们对核酶切割的敏感性。作为对这一想法的检验,两种逆转录病毒载体——一种编码用于切割 lacZ 转录本的锤头核酶,另一种编码 lacZ 信使 RNA——在逆转录病毒包装细胞内共表达。由于逆转录病毒包装信号,核酶预计与含有 lacZ 的病毒基因组 RNA 共定位,但不与 lacZ 信使 RNA 共定位。研究发现,该核酶可将含有 lacZ 的感染性病毒滴度降低 90%,但对 lacZ 信使 RNA 的翻译没有影响。这些结果表明,将基因抑制剂分类到适当的细胞内位点可能会提高其有效性。
Cellular compartmentalization of RNAs is thought to influence their susceptibility to ribozyme cleavage. As a test of this idea, two retroviral vectors-one encoding a hammer-head ribozyme designed to cleave lacZ transcripts and another encoding the lacZ messenger RNA-were coexpressed inside retroviral packaging cells. Because of the retroviral packaging signal, the ribozyme would be expected to colocalize with the lacZ-containing viral genomic RNA but not with the lacZ messenger RNA. The ribozyme was found to reduce the titer of infectious virus containing lacZ by 90 percent, but had no effect on translation of lacZ messenger RNA. These results indicate that sorting gene inhibitors to appropriate intracellular sites may increase their effectiveness.