Inhibition of translation initiation by antisense oligonucleotides via an RNase-H independent mechanism
| Autor: | Victoria Roig, Christian Cazenave, Claudine Boiziau, Robin Kurfurst, Jean-Jacques Toulmé, Nguyen Thanh Thuong |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Xenopus
Molecular Sequence Data Ribonuclease H Eukaryotic translation Reticulocyte Endoribonucleases Genetics Protein biosynthesis medicine Animals Coding region RNA Messenger RNase H Messenger RNA Base Sequence Cell-Free System biology Oligonucleotide Oligonucleotides Antisense Molecular biology Globins Open reading frame medicine.anatomical_structure Protein Biosynthesis biology.protein Female Rabbits |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/19.5.1113 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|