Small non-coding RNAs have been discovered almost two decades ago.  They play crucial roles in regulating development and differentiation,  cellular defense against viruses and in maintaining genomic integrity.  At the core of small RNA pathways lies an effector comples consisting of  the small RNA, which conveys sequence specificity and the associated  Argonatue protein, which is responsible for the effector function. The  best studied small RNAs are microRNAs, which associate with the Ago  clade of Argonaute proteins and regulate gene expression of host genes  through sequence specific interaction with mRNAs leading to  translational inhibition and target destabilization. Small interfering  (si)RNAs are similar in their biogenesis and protein partners to miRNAs  and their main function is believed to be targeting of foreign mRNAs  followed by endonucleolytic cleavage and destruction of target mRNA.  siRNAs have also been extensively used in biomedical research for  sequence-specific knockdown of genes of interest in a process called RNA  interference (RNAi). In S. pombe and plants siRNAs are known to also  act in the nucleus to induce heterochromatinization of targets thereby  leading to transcriptional silencing.

 Recently, a new class of small RNAs, called Piwi-interacting or  piRNAs, has been described. As their name implies, they associate with  the Piwi clade of Argonaute proteins. Piwi proteins and piRNAs are  restricted to the germline of metazoans and they function in a conserved  pathway that is crucial for repressing mobile genomic elements.  Uncontrolled transposon activity leads to mutations and genome  instability. This is especially harmful in germline cells because  germline mutations are transmitted to offspring. Mutations in piwi genes  lead to failure of gametogenesis and sterility in both Drosophila  and mouse. In the cytoplasm piwi proteins mediate cleavage of  transposon transcripts, which are recognized through sequence  complementarity to the piRNAs. Piwi proteins also function in the  nucleus. In both Drosophila and mammals one member of the piwi clade is nuclear. The mouse piRNA pathway was shown to be required for de novo DNA methylation and silencing of TEs. The exact mechanism of this process is, however, not known.