Resistance to Dicer

Dicer is an enzyme present in animal cells that can act on RNA species that have 100% base pairing, to release siRNA species (He and Hannon 2004). Dicer also plays a role in the cleavage of microRNAs. These, like siRNA, are of about 21 nucleotides in length. They are derived from regions of RNA transcripts that have significant levels of intra-molecular base pairing. Such precursors are first cleaved in the nucleus by an enzyme known as drosha (Lee et al. 2003). The fragments produced are frequently RNA hairpins of about 70 nucleotides, with extensive but <100% base pairing. These precursors are cleaved further in the cytoplasm by dicer to release the microRNAs. The similarity between such precursors and the rod-like folding of HDV genomic and antigenomic RNAs is striking and leads to the question of whether HDV RNAs are also cleaved by dicer. Furthermore, there were reports that during the replication of two plant viroids, each with rod-like RNA genomes, that siRNA were detected (Itaya et al. 2001; Martinez De Alba et al. 2002). However, when an examination for siRNA was made for HDV RNAs under various conditions of replication, no siRNA could be detected nor could any siRNA be generated when in vitro transcribed HDV RNA species were subjected to recombinant dicer (Chang et al. 2003).

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