PIWI Proteins and Their Slicer Activity in piRNA Biogenesis and Transposon Silencing

Common to RNAi and related pathways, which are collectively referred to as RNA silencing, is inactivation of cognate RNA targets by small RNA-Argonaute complexes. Small noncoding RNAs of 20-30 nucleotides (nt) in length function as specificity determinants for the repressive activities of Argonaute-containing effector complexes. Argonaute proteins exhibit small RNA-guided RNA endonuclease activity, often referred to as Slicer activity. Animal germline cells express PIWI subclade proteins of the Argonaute superfamily. They bind Piwi-interacting RNAs (piRNAs) to form effector complexes important for germline development and suppress transposon activity to maintain the integrity of the genome in germline cells, both of which are crucial for the success of future generations. In Drosophila ovaries, piRNAs are produced via two distinct pathways: the primary processing and ping-pong cycle pathways. In the ping-pong cycle, PIWI proteins engage in a Slicer-dependent amplification loop between sense and antisense transcripts of a transposon, which consumes transposon sense transcripts (mRNAs), thereby silencing transposons posttranscriptionally. Transposon repressive signals or memory, which initiate the ping-pong cycle, are passed from females to their offspring through the germline transmission of PIWI-piRNA complexes. The ping-pong cycle is conserved among animals, indicating that it arose early in evolution as a form of nucleic acid-based immunity to inactivate transposable elements. The primary processing pathway is a linear Slicer-independent pathway that operates in ovarian somatic cells. piRNAs produced in the primary pathway are exclusively loaded onto Piwi in ovarian somatic cells. Nucleases involved in the pathway have long been sought; recently, a gene named Zucchini was shown to encode a nuclease that processes piRNA intermediates into mature piRNAs.