retrotransposon silencing

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of retrotransposition. Retrotransposons are a subset of transposable elements that use an RNA intermediate and reverse transcribe themselves into the genome. [GOC:dph, GOC:tb, PMID:32823517]

Retrotransposons are mobile genetic elements that can replicate and insert themselves into new locations within the genome. If left unchecked, retrotransposon activity can lead to genomic instability, disrupting gene expression and potentially causing disease. To prevent this, cells have evolved elaborate mechanisms to silence retrotransposons.

One key mechanism involves the RNA interference (RNAi) pathway. This pathway utilizes small RNA molecules, known as short interfering RNAs (siRNAs) or microRNAs (miRNAs), to target and degrade retrotransposon transcripts. These siRNAs are generated by Dicer, an enzyme that cleaves double-stranded RNA into small fragments. The siRNAs are then incorporated into the RNA-induced silencing complex (RISC), which uses the siRNA as a guide to locate and cleave complementary retrotransposon mRNA.

Another important mechanism involves DNA methylation. This process involves the addition of a methyl group to cytosine bases in DNA, typically at CpG dinucleotides. Methylation can repress gene expression, including that of retrotransposons. The methylation pattern is often established during development and maintained by specialized enzymes called DNA methyltransferases. In some cases, methylation can directly inhibit retrotransposon transcription by blocking the binding of transcription factors.

Chromatin modifications also play a role in retrotransposon silencing. Chromatin refers to the complex of DNA and proteins that make up chromosomes. Histone proteins, which are key components of chromatin, can be modified by the addition of chemical groups like acetyl, methyl, or phosphate. These modifications can influence the accessibility of DNA to transcription factors and other regulatory proteins. For example, histone methylation can promote the formation of condensed chromatin, which is associated with gene silencing.

These various mechanisms of retrotransposon silencing often work in concert to ensure genomic stability. For example, RNAi can initiate silencing by degrading retrotransposon transcripts, which then triggers further epigenetic modifications like DNA methylation and histone modifications. These modifications can then reinforce silencing, making it more durable.

The interplay of these mechanisms can be influenced by a range of factors, including the specific type of retrotransposon, the cell type, and environmental conditions. For example, some retrotransposons are particularly active in certain cell types or under specific stress conditions. This highlights the complexity of retrotransposon silencing and the need for a multifaceted approach to ensure their control.'
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Proteins (2)

Compounds (11)