Page last updated: 2024-10-24

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)

ProteinDefinitionTaxonomy
NAD-dependent protein deacetylase sirtuin-7An NAD-dependent protein deacetylase sirtuin-7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NRC8]Homo sapiens (human)
NAD-dependent protein deacetylase sirtuin-6An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
pyrazinamidepyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis.monocarboxylic acid amide;
N-acylammonia;
pyrazines
antitubercular agent;
prodrug
pyrazinoic acidpyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide.

pyrazinoic acid: active metabolite of pyrazinamide; structure
pyrazinecarboxylic acidantitubercular agent;
drug metabolite
1-(4-nitrophenyl)piperazine1-(4-nitrophenyl)piperazine: structure in first source
rubimaillinrubimaillin : A benzochromene that is 2H-benzo[h]chromene which is substituted by two methyl groups at position 2, a methoxycarbonyl group at position 5, and a hydroxy group at position 6. Found in the Chinese medical plant Rubia cordifola, It has an anti-cancer effect by inhibition of TNF-alpha-induced NF-kappaB activation. It is also a dual inhibitor of acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), but is more selective for the ACAT2 isozyme.

rubimaillin: structure given in first source
benzochromene;
methyl ester;
phenols
acyl-CoA:cholesterol acyltransferase 2 inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
neuroprotective agent;
NF-kappaB inhibitor;
plant metabolite
5-chloropyrazinamide
trichostatin atrichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCESantibiotic antifungal agent;
hydroxamic acid;
trichostatin
bacterial metabolite;
EC 3.5.1.98 (histone deacetylase) inhibitor;
geroprotector
(3R,5S)-fluvastatin(3R,5S)-fluvastatin : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which the stereocentres beta- and delta- to the carboxy group have R and S configuration, respectively. The drug fluvastatin is an equimolar mixture of this compound and its enantiomer.(6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid;
statin (synthetic)
panobinostatpanobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.

Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.
cinnamamides;
hydroxamic acid;
methylindole;
secondary amino compound
angiogenesis modulating agent;
antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
quisinostatindoles
ly2784544pyridazines