Natural occurrence of antisense RNA and its role in gene regulation have been realised long ago. Gene expression in both prokaryotes and eukaryotes are controlled by the product of regulatory gene, which are supposed to be proteins only.
Recently, naturally occurring regulatory gene that directs the synthesis of RNA which can control gene expression. This newly discovered RNA repressor can control gene expression. This regulatory RNA once again contains a sequence that is complementary to the target RNA and base pairs occur.
The term antisense has been coined to refer this regulatory RNA and the genes that are direct to the synthesis of antisense RNA (occur naturally) are designated as antisense genes.
Occurrence of Antisense RNA in Prokaryotes:
Antisense genes were initially discovered in prokaryotes with short period of time. Antisense RNA has been identified and proved its complex role in the regulation of replication in bacteria such as plasmid replication, osmoregulation of porin expression etc. (Fig. 22.1).
Fig. 22.1 Antisense RNA synthesis in bacteria
An important discovery about natural biological functions of antisense molecule was made in 1981 by Jun-Ichi Tomizawa at the National Institute of Health (NIH). Tomizowa discovered that number of plasmid copy number in bacteria (ColE1) depends on the number of available RNA primer and its availability is controlled not by their total concentration but rather by the ratio of primers to specific inhibitor molecule.
This inhibitor molecule was later found to be RNA molecule transcribed from the DNA strand complementary to the one that produces the RNA primer. Subsequently, additional regulation of transcription by antisense RNA was evidenced in bacteria.
Interaction of small antisense RNA to the primer precursor inhibits formation of a unique structure. It assumes unique structure during its synthesis. The rate of RNA-RNA interaction is originally important for effective regulation by antisense RNA and kinetics of RNA-RNA interactions depends on the complex folded nature of RNA.
Occurrence of Antisense RNA in Eukaryote System:
Naturally occurring antisense RNA regulation have not been recorded in eukaryote system. However, there are several cases known in eukaryote system in which both strands of DNA segments are transcribed or complementary RNAs have been detected.
Synthesis of a RNA species complementary to the barley alpha-amylase mRNA is well regulated. The antisense RNA plays a important regulatory role in blocking the expression of alpha-amylase and protecting the storage content to seed.
Certain surprising results in human exploration on antisense RNA suggested that approximately 1% of human genes estimated to be undergoing transcription from both strands. Evidence based on expressed sequence tag (ESI) datasets and other validation test also reveals that approximately 3,000 genes are going with probable antisense expression and atleast 8% of the estimated 40,000 human genes are influenced by antisense.