The integrity of the germline genome must be maintained to achieve successive generations of a species, because germline cells are the only source for transmitting genetic information to the next generation. Accordingly, the germline has acquired a system dedicated to protecting the genome from ‘injuries’ caused by harmful selfish nucleic acid elements, such as TEs (transposable elements). Accumulating evidence shows that a germline-specific subclass of small non-coding RNAs, piRNAs (piwi-interacting RNAs), are necessary for silencing TEs to protect the genome in germline cells. To silence TEs post-transcriptionally and/or transcriptionally, mature piRNAs are loaded on to germline-specific Argonaute proteins, or PIWI proteins, to form the piRISC (piRNA-induced silencing complex). The present chapter will highlight insights into the molecular mechanisms underlying piRISC-mediated silencing and piRNA biogenesis, and discuss a possible link with tumorigenesis, particularly in Drosophila.

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