negative regulation of miRNA-mediated gene silencing

Definition

Target type: biologicalprocess

A process that decreases the rate, frequency, or extent of gene silencing by a microRNA (miRNA). [GOC:aruk, GOC:bc, GOC:dph, GOC:rl, GOC:tb, PMID:23985560, PMID:28379604]

Negative regulation of miRNA-mediated gene silencing involves a complex interplay of molecular mechanisms that counteract the silencing effects of microRNAs (miRNAs). miRNAs are small non-coding RNAs that bind to the 3' untranslated region (3'UTR) of target mRNAs, leading to translational repression or mRNA degradation. However, cells possess intricate pathways to fine-tune and modulate this silencing process.

One prominent mechanism involves **competing endogenous RNAs (ceRNAs)**, which act as decoys for miRNAs. These ceRNAs share miRNA binding sites with target mRNAs, sequestering miRNAs and preventing their binding to the target transcripts. This competition reduces the availability of miRNAs for silencing, effectively elevating the expression of the target gene.

**RNA-binding proteins (RBPs)** also play a crucial role in modulating miRNA-mediated silencing. Some RBPs can directly interact with miRNAs, inhibiting their association with target mRNAs. Others can bind to the 3'UTR of target transcripts, masking the miRNA binding sites or promoting the degradation of the miRNA-mRNA complex.

**Epigenetic modifications**, such as methylation and acetylation, can influence the accessibility of miRNA binding sites. DNA methylation can silence genes by blocking miRNA binding, while histone acetylation can enhance miRNA binding and increase silencing.

**Cellular stress response pathways** also contribute to the regulation of miRNA-mediated gene silencing. In response to stress, cells can activate signaling pathways that alter the expression or activity of miRNA processing machinery, miRNA-binding proteins, or target mRNAs.

Furthermore, **miRNA-induced silencing complex (RISC) components** themselves can be subject to regulation. Factors involved in RISC assembly or stability can influence the efficiency of miRNA-mediated silencing.

Overall, negative regulation of miRNA-mediated gene silencing is a dynamic and intricate process involving a diverse array of molecular mechanisms. This intricate regulation ensures that miRNA-mediated silencing is appropriately fine-tuned in response to cellular needs and environmental stimuli.'
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Proteins (1)

Compounds (3)