Rna Decoys

In contrast to ribozymes and antisense RNAs, RNA decoys do not attack the viral RNAs directly. RNA decoys are mutant RNAs that resemble authentic viral RNAs that have crucial functions in the viral life cycle. They mimic such RNA structures and decoy viral and/or cellular factors required for the propagation of the virus.3044-53 For example, HIV-1 replication largely depends on the two regulatory proteins Tat and Rev. These proteins bind to specific regions in the viral RNA, which are termed TAR and RRE, respectively. Cells that overexpress short RNAs containing TAR or RRE sequences will capture Tat or Rev proteins, preventing the binding of such proteins to their actual targets. This strategy has the advantage over antisense RNAs and ribozymes in that mutant Tat or Rev, which will not bind to the RNA decoys, will also not bind to their actual targets. Thus, the likelihood is low that mutant strains would arise which would bypass the RNA decoy trap. However, it still remains to be elucidated whether cellular factors also bind to Tat or Rev decoys, and whether overexpression of decoy RNAs would lead to the sequestering of the resulting protein-RNA complexes in the cell.

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