Rna Interference Regulates Gene Expression

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Chapter 1: Introduction

1.1 RNA interference regulates gene expression in eukaryotes

The flow of genetic information within a living organism was first stated by Crick as “DNA makes RNA and RNA makes protein” (Crick 1956). In response to environmental stimuli, the dynamic modulation of specific gene products (mRNAs and proteins) confers flexibility and adaptability to prokaryotes, eukaryotes, and viruses (Crick 1956). Proper gene regulation is essential for cell growth, development, proliferation, and differentiation, which also lead to the creation of distinct cell types and cell cycle stages that share the same genome but exhibit different gene expression profiles (Chen and Rajewsky 2007). The increase or decrease of a certain gene
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1998). Interestingly, the phenomenon that the introduction of double-stranded RNAs “quelled” the expression of endogenous genes contain homologous sequences had been observed and even utilized as a tool to knock down gene expression by researchers long before the underlying RNAi mechanism was identified and separated from the antisense silencing by Fire and Mello in 1998 (Fire et al. 1998). They consistently found that the introduction of double-stranded RNAs (dsRNAs) was 100 or more folds effective than the single-stranded “sense” or “antisense” RNAs (ssRNA) to silence the complement gene expression (Fire et al. 1998; Kennerdell and Carthew 1998). Moreover, the dsRNA mediated gene silencing can be transferred between adjacent cells, and even inherited through multiple rounds of cell division (Fire et al. 1998). Therefore, it is proposed that this so called “RNA interference” is an inheritable and transferrable process that involves a catalytic process, which differs from the previously known antisense silencing that ssRNAs directly bind to the complement mRNA targets to repress translation by blocking ribosome access. Subsequently, Tuschl and co-workers demonstrated that RNAi mechanism exists in mammalian cell lines for the introduction of synthetic
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