Viruses and RNA interference in mammalian cells

RNAi
The development of biotechnological methods of research in the last years made possible
RNA interference to be discovered. RNAi is a regulatory mechanism, which silences genes
degrading mRNA in a sequence-specific manner with help of small pieces of doublestranded
RNAs: small or short interfering RNAs (siRNAs) and micro RNAs (miRNAs). It
suppresses gene expression at the translation stage or by interfering the transcription of
specific genes. RNAi has been observed in organisms as diverse as plants, protozoa,
nematodes, fungi, insects, and mammals (Hu et al., 2004). This process takes an integral part
in various eukaryotic functions such as viral defense, chromatin remodeling, genome
rearrangement, developmental timing, brain morphogenesis and stem cell maintenance
(MacRae et al., 2006).
2. RNA interference
History of discovery
The history of RNAi discovery started when scientists tried to compare the activity of
silencing of antisense or sense single-stranded RNAs (ssRNAs) with their double-stranded
RNA (dsRNA) hybrid in two types of experiments in 1990. First group of experiments was
made to estimate antisense suppression for selective silencing of plant gene expression. In
theory, antisense RNA encoded by a transgene should prevent translation of complementary
mRNA of a plant gene into protein by basepairing to it. But the control “sense” transgene
RNAs are unable to do it, because they can not basepair to mRNA. Hence, the silencing
should not been observed, but surprisingly it was (Smith et al., 1990). The other type of
experiments, has led to the conclusion that the expression of both introduced and
homologous endogenous genes in petunia leaves was suppressed by introduction of a
pigment-producing gene that was under a control of a powerful promoter. This phenomenon
scientist called “co-suppression”. It was discovered while scientists made the efforts to
enhance coloration of petunia flowers. They tried to overexpress a transgene that encoded a
protein involved in a synthesis of pigments. However, it led to a partial or complete color
loss. That was the result of “co-suppression” or coordinate silencing (Napoli et al., 1990;
Van der Krol et al., 1990). “Co-suppression” also occurs at the post-transcriptional level.
Such post-transcriptional gene silencing (PTGS) in plants is equivalent of RNAi. Posttranscriptional
gene silencing is a mechanism involving dsRNA, nucleases, small RNAs and
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