Modulation of double-stranded RNAs in vivo by RNA duplex unwindase

The double-stranded RNA (dsRNA) unwinding/modifying activity is a recently discovered cellular activity capable of unwinding or denaturing dsRNAs by modifying multiple adenosine residues to inosines and creating I-U mismatched base-pairings. The biological functions of this activity, which can potentially mutate the coding capacity of messenger RNAs (mRNAs), are presently not known. However, this unwinding/modifying activity is likely to affect the secondary structures, processing, and turn-over of various eukaryotic as well as viral transcripts. Although the activity was originally found and proposed as a cellular factor that interfered with the use of antisense RNA, it now appears more likely that the activity in fact may participate in antisense RNA suppression of target genes, either by altering the coding capacity of the sense mRNAs or by accelerating the degradation of duplex RNAs. Further understanding of this novel enzymatic activity, and thus, in turn, of the metabolism of dsRNAs in vivo, should allow us to derive a better strategy for designing antisense RNA.