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A non-coding RNA (ncRNA) is a functional RNA molecule that is transcribed from DNA but not translated into proteins. Epigenetic related ncRNAs include miRNA, siRNA, piRNA and lncRNA. In general, ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Those ncRNAs that appear to be involved in epigenetic processes can be divided into two main groups; the short ncRNAs (<30 nts) and the long ncRNAs (>200 nts). The three major classes of short non-coding RNAs are microRNAs (miRNAs), short interfering RNAs (siRNAs), and piwi-interacting RNAs (piRNAs). Both major groups are shown to play a role in heterochromatin formation, histone modification, DNA methylation targeting, and gene silencing.
MicroRNAs (miRNA) generally bind to a specific target messenger RNA with a complementary sequence to induce cleavage, or degradation or block translation. This may be done in the context of a feedback mechanism that involves chromosome methylation. For example, miRNA genes mir-127 and mir-136 were found to be involved in regulating the genetic imprinting of Rtl1, a key gene involved in placenta formation in mice. Methylation of a specific region in the paternal chromosome results in expression of Rtl1. If the chromosome is not methylated, as on the maternal chromosome, mir-127 and mir-136 are produced and bind to the Rtl1 transcript and induce degradation. Lack of Rtl1 protein expression due to improper epigenetic modifications can result in fetal death in mice.
Short interfering RNAs (siRNA) function in a similar way as miRNAs to mediate post-transcriptional gene silencing (PTGS) as a result of mRNA degradation. In addition to this function, siRNAs have also been shown to induce heterochromatin formation via an RNA-induced transcriptional silencing (RITS) complex which when bound to siRNA promotes H3K9 methylation and chromatin condensation.
Piwi-interacting RNAs (piRNA) are so named due to their interaction with the piwi family of proteins. The primary function of these RNA molecules involves chromatin regulation and suppression of transposon activity in germline and somatic cells. PiRNAs that are antisense to expressed transposons target and cleave the transposon in complexes with PIWI-proteins. This cleavage generates additional piRNAs which target and cleave additional transposons. This cycle continues to produce an abundance of piRNAs and augment transposon silencing.