Discoveries over the past decade portend a paradigm shift in molecular biology. Evidence suggests that RNA is not only functional as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression, which is increasingly elaborate in complex organisms. Regulatory RNA seems to operate at many levels; in particular, it plays an important part in the epigenetic processes that control differentiation and development. These discoveries suggest a central role for RNA in human evolution and ontogeny. Here, we review the emergence of the previously unsuspected world of regulatory RNA from a historical perspective.

Gene regulation, the ability to control whether a gene is expressed or not, is critical in controlling cellular and metabolic processes and contributes to diversity and variation in organisms. Furthermore, it is the key determinant in cellular differentiation and morphogenesis. There are specific types of RNA molecules that can be utilized to control gene regulation, including messenger RNAs (mRNAs), small RNAs such as microRNAs and lastly, antisense RNAs. The following is a brief overview of antisense RNAs and their role in RNA regulation. Antisense RNAs have been recently investigated as a new class of antiviral drugs.

Antisense RNAs are single-stranded RNA molecules that exhibit a complementary relationship to specific mRNAs. Antisense RNAs are utilized for gene regulation and specifically target mRNA molecules that are used for protein synthesis. The antisense RNA can physically pair and bind to the complementary mRNA, thus inhibiting the ability of the mRNA to be processed in the translation machinery. Pairing antisense RNA is a technique that can be utilized within the laboratory for gene regulation — however, it is not without limitations. Naturally occurring antisense RNAs have been isolated in a various microbes, including the E. coli RI plasmid, which uses a hok/sok system. A hok/sok system is a mechanism employed by E. coli that is used as a postsegregational killing mechanism. The hok gene is a toxic gene and the sok gene is an antitoxin. Hence, E. coli utilizing this system can regulate the expression of hok (toxin) and inhibits its translation by producing sok RNA (antitoxin). The outcome is the repression of hok mRNA translation.

After the elucidation of the double-helical structure of DNA in 19535, the following years were preoccupied with deciphering the ‘genetic code’ and establishing the mechanistic pathway between gene and protein: the identification of a transitory template (mRNA), an adaptor (tRNA) and the ‘ribosome’ factory comprised of ribosomal proteins and RNA (rRNA) for the translation of the code into a polypeptide. In 1958, Crick published the celebrated ‘central dogma’ to describe the flow of genetic information (DNA → RNA → protein), which has proved remarkably accurate and durable, including the prediction of reverse transcription6. Nonetheless, in conceptual terms, RNA was tacitly consigned to be the template (and infrastructural platform – ribosomal and transfer RNAs) for protein synthesis or, at least, has been interpreted in this way by most people since that time.

Conclusion

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