Antisense RNA Structure and Function

Abstract

Antisense RNAs are small, diffusible, regulatory RNAs that bind to complementary regions on specific target RNAs to control their biological function at a posttranscriptional level. Most have been identified in prokaryotic organisms, but a few putative eukaryotic cases have been described. The biological systems involved are varied and interesting in their own rights. Antisense and target RNAs are often, but not necessarily, transcribed in opposite directions from the same DNA template, yielding counter-transcripts that are completely complementary across a defined region. However, complementarity need not be complete, and antisense RNAs can be transcribed from regions unlinked to those of their target RNAs. Artificial antisense RNAs have been used for a variety of research purposes, and there is considerable interest in their development for therapeutic applications.

Here, we are concerned with the structure of antisense and target RNAs, with special emphasis on how these structures determine the pathways of RNA/RNA pairing. Our discussion is primarily limited to the best-characterized natural examples, which derive from prokaryotic accessory elements (phage, plasmids, and transposons). In these cases, the RNAs are all expressed as counter-transcripts. The antisense RNAs are small (67–108 nucleotides) and contain one to three stem-loop secondary structural elements, which are essential for their function. The target RNAs are longer and may contain complementary secondary structures, in addition to others, which are equally important. Stable complexes between antisense and target RNAs are essentially irreversible under physiological conditions and are most easily detected as persistent bimolecular complexes on semi-denaturing gels. However, stable complexes...