Gene silencing is a process in genetics in which genes are actively switched off. Gene silencing serves to regulate the activity of genes (gene regulation). In gene silencing, gene regulation is achieved by inhibiting the transfer (transcription) of genetic information from DNA to mRNA (transcriptional gene silencing) or the subsequent translation of the information stored on the mRNA into a protein (post-transcriptional gene silencing).
Gene-Silencing
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Transcriptional gene silencing: Transcriptional gene silencing is a result of epigenetic modifications of DNA, such as DNA methylation or histone modifications in particular. The modifications of the histone ends create a kind of heterochromatic state around the gene, which prevents the transcription machinery (RNA polymerase, transcription factors, etc.) from binding.
Post-transcriptional gene silencing: Post-transcriptional gene silencing (PTGS) refers to the processes of gene silencing that occur only after the genetic information has been transcribed from DNA to the transferring mRNA. In particular, the forms of post-transcriptional gene silencing include nonsense-mediated mRNA decay (NMD) and RNA interference (RNAi).
While nonsense-mediated mRNA decay primarily serves to prevent nonsense point mutations, RNA interference is a predominantly regulatory process involving specific RNA molecules, such as miRNA (micro RNA) and siRNA (small interfering RNA). Post-transcriptional gene silencing can lead to intensified degradation of the mRNA of a particular gene. The degradation of the mRNA prevents translation and thus the formation of the specific gene product (usually a protein). In addition, gene-specific direct inhibition of translation is possible as a result of post-transcriptional gene silencing.
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It is assumed that gene silencing is actually a defence mechanism directed against plant viruses (plant defence). Thus, the plant is able to specifically recognize large amounts of a certain transcript and degrade it.
The specificity of this process is still largely unclear. However, secondary structures of the mRNA (e.g. hairpin loops on palindromic sequences) seem to play an important role in recognition. However, the cell's own homologue is also recognized and destroyed, so that instead of the expected overexpression of a certain protein, its complete failure is observed.
In the meantime, however, silencing is increasingly being used to specifically silence individual genes so that their biological significance can be investigated via the function that is then lost. This is done by implementing short fragments that are complementary to parts of the gene. In this way, double-stranded regions are specifically induced on the mRNA read from this gene, which then cause the degradation of this DNA (so-called RNAi technique).saRNA also opens up a therapeutic potential, e.g. in the treatment of malignancies through targeted activation of tumor suppressor genes (Ren S et al. 2013).
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- Filipowicz, W. et al. (2005): Post-transcriptional gene silencing by siRNAs and miRNAs. Curr. Opin. Struct. Biol. 15(3):331-41. PMID 15925505 doi:10.1016/j.sbi.2005.05.006 PDF
- Pushparaj PN et al. (2008) RNAi and RNAa -- the yin and yang of RNAome. Bioinformation. 2008 Jan 11;2(6): 235-237
- Place RF et al. (2010) Defining features and exploring chemical modifications to manipulate RNAa activity. Curr Pharm Biotechnol11: 518-526.
- Ren S et al (2013) Targeted induction of endogenous NKX3-1 by small activating RNA inhibits prostate tumor growth. Prostate 73:1591-1601.