Molecular Biology: Mechanism of Gene Silencing

There are around 30-40 trillion cells in the human body. Each cell consists of an outer membrane, cytoplasm, and nucleus, which controls the activity of the rest of the cell. DNA (deoxyribonucleic acid), which contains the ‘genetic code' of living things, is located in the nucleus.

DNA remains confined to the nucleus of the cell and it relies on another molecule, RNA, to deliver its instructions and translate them into action. When the instructions are turned into a functional product, such as a protein, this is called gene expression. Gene silencing is generally defined as an epigenetic modification of gene expression leading to inactivation of previously active individual genes.

Gene silencing makes use of the body's natural processes to control disease by suppressing or ‘silencing' specific genes that are associated with certain diseases. In this context, ‘silencing' means temporarily blocking a specific gene's message that would otherwise trigger an unwanted effect. It is considered a gene knockdown mechanism since the methods used to silence genes generally reduce the expression of a gene by at least 70% but do not eliminate it.

Gene silencing occurs via transcriptional gene silencing (TGS) and post-transcriptional gene silencing (PTGS). Transcriptional gene silencing (TGS) is a nuclear-localized mechanism, which quenches transcription by blocking a promoter region for the binding of transcriptional machinery. Different methods of TGS are RNA-directed DNA methylation (RdDM), genomic imprinting, paramutation, transposon silencing, and position effect.