Genesilencing

Gene silencing is the regulation of gene activity so that the amount or function of its product is reduced or suppressed. It includes transcriptional gene silencing, which decreases transcription, and post-transcriptional gene silencing, which acts on RNA after it is produced.

In post-transcriptional gene silencing, small RNA molecules such as small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide an effector complex, typically the RNA-induced silencing complex (RISC), to target mRNAs for degradation or translational repression. In transcriptional gene silencing, small RNAs can direct chromatin modifications and DNA methylation through pathways such as RNA-directed DNA methylation (RdDM), leading to condensed chromatin and reduced transcription.

Gene silencing plays important roles in development, gene regulation, and defense against transposons and viruses. It can be genome-wide or gene-specific and often varies by tissue or developmental stage. Experimental and practical applications leverage these natural mechanisms to study gene function or treat diseases, as well as to modify traits in crops.

Common approaches include RNA interference using siRNA or short hairpin RNA (shRNA), antisense oligonucleotides, and emerging methods such as CRISPR interference (CRISPRi) and targeted epigenetic editing. These tools enable knockdown or repression of specific genes, either temporarily or durably, depending on the strategy.

The discovery of RNA interference in 1998 by Fire and Mello highlighted a fundamental gene-regulatory pathway. Challenges for therapeutic and agricultural use include off-target effects, delivery and stability of silencing agents, and variable efficacy in living organisms. Nevertheless, gene silencing has become integral to functional genomics, biotechnology, and medicine, with several approved RNAi therapies and ongoing research in diverse fields.