Gene silencing

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Gene regulation
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Transcriptional gene silencing
Post-transcriptional gene silencing
Gene Ontology
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The gene silencing ( gene silencing ) is a process from the Genetics , wherein the gene expression is reduced. In gene silencing, gene regulation takes place by inhibiting the transfer ( transcription ) of genetic information from the DNA to the mRNA (transcriptional gene silencing) or the subsequent translation ( translation ) of the information stored on the mRNA into a protein (post-transcriptional Gene silencing).

Transcriptional gene silencing

Transcriptional gene silencing is a result of epigenetic changes in DNA (such as DNA methylation or histone modifications ) or the binding of repressors to a silencer or non-coding ribonucleic acids . By modifying the ends of the histones, a kind of heterochromatic state is created around the gene, which prevents the transcription machine ( RNA polymerase , transcription factors, etc.) from binding. The classic example is the phenomenon known as position effect variegation (PEV). It changes the state of chromatin and thus controls the transcription activity of the affected gene or gene region.

Post-transcriptional gene silencing

Mechanism of post-transcriptional gene silencing by RNA interference

Post-transcriptional gene silencing (PTGS) refers to the processes that only take place after the genetic information has been transcribed from the DNA to the transmitted mRNA, e.g. B. before and during translation . The forms of post-transcriptional gene silencing include in particular nonsense-mediated mRNA decay (NMD) and RNA interference (RNAi). While the nonsense-mediated mRNA decay is primarily used to avoid nonsense point mutations , the RNA interference is a predominantly regulatory process involving specific RNA molecules such as miRNA and siRNA . Post-transcriptional gene silencing can lead to an intensified breakdown of the mRNA of a particular gene. The degradation of the mRNA prevents translation and thus the formation of the specific gene product (usually a protein ). In addition, a gene-specific direct inhibition of translation as a result of post-transcriptional gene silencing is possible.

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Individual evidence

  1. ↑ N. Reynolds, A. O'Shaughnessy, B. Hendrich: Transcriptional repressors: multifaceted regulators of gene expression. In: Development. Volume 140, number 3, February 2013, pp. 505-512, doi: 10.1242 / dev . 083105 . PMID 23293282 .
  2. ↑ B. Malecová, K. Morris: Transcriptional gene silencing through epigenetic changes mediated by non-coding RNAs. In: Current opinion in molecular therapeutics. Volume 12, Number 2, April 2010, pp. 214-222, PMID 20373265 . PMC 2861437 (free full text).
  3. ↑ W. Filipowicz et al. : Post-transcriptional gene silencing by siRNAs and miRNAs. In: Curr. Opin. Struct. Biol. 2005, 15, 3, pp. 331-41. PMID 15925505 doi: 10.1016 / j.sbi.2005.05.006 .
  4. ↑ AE Martínez de Alba, E. Elvira-Matelot, H. Vaucheret: Gene silencing in plants: a diversity of pathways. In: Biochimica et Biophysica Acta . Volume 1829, number 12, December 2013, pp. 1300–1308, doi: 10.1016 / j.bbagrm.2013.10.005 . PMID 24185199 .
  5. ↑ KV Morris: RNA-directed transcriptional gene silencing and activation in human cells. In: Oligonucleotides . Volume 19, number 4, December 2009, pp. 299-306, doi: 10.1089 / oli.2009.0212 . PMID 19943804 . PMC 2861411 (free full text).