RNA-induced transcriptional silencing

RNA-induced transcriptional silencing (RITS) is a form of RNA interference by which short RNA molecules - microRNA (miRNA) or small interfering RNA (siRNA) - trigger the downregulation of transcription of a particular gene or genomic region. This is usually accomplished by modification of histones, often by methylation, or by the induction of heterochromatin formation. The protein complex that binds the miRNA and interacts with histones and DNA is known as the RITS complex.

RITS has been studied extensively in the fission yeast S. pombe, particularly the induction and spreading of heterochromatin in the mating-type region and in centromere formation. The RITS complex in S. pombe contains at least a piwi domain-containing RNase H-like argonaute, a chromodomain protein Chp1, and a protein called Tas3 of unknown function, while heterochromatin formation has been shown to require at least argonaute and an RNA-dependent RNA polymerase. Loss of these genes in S. pombe results in abnormal heterochromatin organization and formation of the chromosome centromeres, resulting in slow or stalled anaphase during cell division.

The maintenance of heterochromatin regions by RITS complexes has been described as a self-reinforcing feedback loop, in which RITS complexes stably bind the methylated histones of a heterochromatin region and induce co-transcriptional degradation of any nascent messenger RNA (mRNA) transcripts, which are then used as RNA-dependent RNA polymerase substrates to replenish the complement of siRNA molecules. Heterochromatin formation, but possibly not maintenance, is dependent on the ribonuclease protein dicer, which is used to generate the initial complement of siRNAs.

The relevance of observations from fission yeast mating-type regions and centromeres to mammals is not clear, as some evidence suggests that heterochromatin maintenance in mammalian cells is independent of the components of the RNAi pathway.