ANTISENSE AND ANTIGENE PROPERTIES OF PEPTIDE NUCLEIC-ACIDS

ANTISENSE AND ANTIGENE PROPERTIES OF PEPTIDE NUCLEIC-ACIDS
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DOI:
10.1126/science.1279811
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发表时间:
1992-11-27
期刊:
影响因子:
56.9
通讯作者:
BABISS, LE
BABISS, LE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HANVEY, JC;PEFFER, NJ;BABISS, LE

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肽核酸(PNAs)是聚酰胺低聚物,它能够链侵入双链DNA,导致一条DNA链被置换并形成D环。无论是T10肽核酸还是混合序列的15聚体肽核酸与无G转录盒的转录链结合,都会导致聚合酶II转录延伸90% - 100%的位点特异性终止。当T10肽核酸结合在非转录链上时,位点特异性抑制从未超过50%。肽核酸与RNA结合会导致逆转录和体外翻译在肽核酸·RNA异源双链的位置发生位点特异性终止。向持续表达SV40大T抗原(T Ag)的细胞中进行核微注射靶向T Ag信使RNA的15聚体或20聚体肽核酸,会抑制T Ag的表达。这种效应是特异性的,因为共注射的表达载体中β - 半乳糖苷酶的表达没有降低,并且微注射10聚体肽核酸后T Ag的表达没有受到抑制。
Peptide nucleic acids (PNAs) are polyamide oligomers that can strand invade duplex DNA, causing displacement of one DNA strand and formation of a D-loop. Binding of either a T10 PNA or a mixed sequence 15-mer PNA to the transcribed strand of a G-free transcription cassette caused 90 to 100 percent site-specific termination of pol II transcription elongation. When a T10 PNA was bound on the nontranscribed strand, site-specific inhibition never exceeded 50 percent. Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation, precisely at the position of the PNA . RNA heteroduplex. Nuclear microinjection of cells constitutively expressing SV40 large T antigen (T Ag) with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression. This effect was specific in that there was no reduction in beta-galactosidase expression from a coinjected expression vector and no inhibition of T Ag expression after microinjection of a 10-mer PNA.