RNAi: a discovery that revolutionized biomedical researches

One of the most important breakthroughs in modern biology was discovering that double chain small or large RNA molecules are able to regulate gene expression. Formerly it was thought RNAs have just two broad functions in cells: Single-stranded messenger RNAs (mRNAs) are vital intermediaries in gene expression, transmitting information between DNA and protein. Ribosomal and transfer RNAs have structural, catalytic and information-decoding roles in the process of protein synthesis [1, 2]. In 1998 Fire and Mello observed in Caenorthabditis elegans that double-stranded RNA (dsRNA) was the source of sequence-specific inhibition of protein expression, which they called RNA interference (RNAi) [3]. This phenomenon was observed at first time in plants. In early 90 ́s plant biologists working with petunias found that introducing numerous copies of a gene that codes for deep purple flowers led to an even darker purple hue, but rather to plants with white or patchy flowers [4]. That indicated that both transgenes and plants genes have been suppressed. However, this phenomenon was not well understood until Fire and Mello published their results. A great advance in this field was produced when similar process of gene silencing observed in plants and C. elegans were reported in many others eukaryotes resulting in an evolutionarily ancient mechanism in numerous organisms including insects, fungi, mammalian and others. Determining the presence of this phenomenon in mammalian was a hard work due to the interferon response against dsRNA larges which induce non specific degradation of mRNA. Interferon triggers the degradation of mRNA by inducing 2-5 oligoadenylate synthase which actives RNAse L. In addition interferon activates PKR leading to a global inhibition of mRNA translation [5]. Nevertheless, in 2001 Tuschl and colleagues introduced chemically synthesized small interfering RNA (siRNA) into mammalian cells and showed sequencing specific silencing of gene expression in several mammalian cell lines without nonspecific effects [6, 7]. Although the gene silencing presents differences in animals, fungi and plants, the process and its molecular participants are basically the same. It is considered that this is an ancestral process to which a function of maintenance of the integrity of the genome is attributed since it suppresses the transposon mobilization, the accumulation of repeated DNA in the germ line; it destroys aberrant, incomplete or unstable messenger RNA and it also works naturally against the viral infections constituting a defense mechanism in many organisms [1, 8]. It is known that the inhibition of gene expression triggered by small interference RNA can take place at three levels; they are: the transcriptional, the post transcriptional and the translational level.