MECHANISM OF INHIBITION OF MESSENGER-RNA TRANSLATION BY ANTISENSE OLIGONUCLEOTIDES - BRIEF REVIEW

Oligonucleotides inhibit the translation of mRNAs by binding complementary sequences present at their 5' end, and in the region of the initiator codon. In the presence of ribonuclease H, degradation causes the inhibition of translation by deoxyribooligonucleotides or their phosphorothioate analogs that are complementary to either the 5' end of the molecules or to the coding region. This mechanism that enhances the inhibitory effect does not function in the case of oligonucleoside methylphosphonates or oligonucleotides synthesized from alpha-nucleosides; the complexes that these form with RNA do not serve as substrates for ribonuclease H. The efficiency of inhibition is determined by the length of the oligonucleotide and the structure of the mRNA target region. The inhibitory characteristics of oligonucleotides may be enhanced by the introduction into their structure of intercalating and reactive groups.