INHIBITION OF TRANSLATION INITIATION BY ANTISENSE OLIGONUCLEOTIDES VIA AN RNASE-H INDEPENDENT MECHANISM

被引：138

作者：

BOIZIAU, C

KURFURST, R

CAZENAVE, C

ROIG, V

THUONG, NT

TOULME, JJ

机构：

[1] MUSEUM NATL HIST NAT,BIOPHYS LAB,F-75231 PARIS 05,FRANCE

[2] CNRS,CTR BIOPHYS MOLEC,F-45071 ORLEANS 02,FRANCE

来源：

NUCLEIC ACIDS RESEARCH | 1991年 / 19卷 / 05期

关键词：

D O I：

10.1093/nar/19.5.1113

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have used alpha-oligomers as antisense oligonucleotides complementary to three different sequences of the rabbit beta-globin mRNA: a region adjacent to the cap site, a region spanning the AUG initiation codon or a sequence in the coding region. These alpha-oligonucleotides were synthesized either with a free 5' OH group or linked to an acridine derivative. The effect of these oligonucleotides on mRNA translation was investigated in cell-free extracts and in Xenopus oocytes. In rabbit reticulocyte lysate and in wheat germ extracts oligomers targeted to the cap site and the initiation codon reduced beta-globin synthesis in a dose-dependent manner, whereas the target mRNA remained intact. The anti-cap alpha-oligomer was even more efficient that its beta-counterpart in rabbit reticulocyte lysate. In contrast, only the alpha-oligomer, linked to the acridine derivative, complementary to the cap region displayed significant antisense properties in Xenopus oocytes. Therefore initiation of translation can be arrested by oligonucleotide/RNA hybrids which are not substrates for RNase-H.

引用

页码：1113 / 1119

页数：7

共 38 条

[1] NUCLEIC-ACID BINDING-MOLECULES WITH HIGH-AFFINITY AND BASE SEQUENCE SPECIFICITY - INTERCALATING AGENTS COVALENTLY LINKED TO OLIGODEOXYNUCLEOTIDES [J].