Title: piRNA Biogenesis in Drosophila melanogaster
Abstract: The chromatin structure of genomic regions giving rise to piRNAs is crucial for piRNA biogenesis. Counterintuitively, piRNA biogenesis depends on the presence of the allegedly repressive histone 3 lysine 9 tri-methylation (H3K9me3) mark on dual-strand piRNA clusters. Establishment of proper chromatin on dual-strand clusters requires trans-generational inheritance of homologous piRNAs. The function of dual-strand clusters as memory banks of previous transposon invasions requires the presence of chromatin-bound proteins, which modulate transcription initiation and termination from these loci as well as splicing of, and TREX loading on, nascent piRNA precursor transcripts. piRNAs can be processed from precursors by the endonuclease Zucchini (Zuc) or by Piwi proteins guided by complementary piRNAs (ping-pong). Recent studies revealed that Zuc-dependent processing, which was considered the primary mechanism, can be triggered by ping-pong. The PIWI-interacting RNA (piRNA) pathway is a conserved defense system that protects the genome integrity of the animal germline from deleterious transposable elements. Targets of silencing are recognized by small noncoding piRNAs that are processed from long precursor molecules. Although piRNAs and other classes of small noncoding RNAs, such as miRNAs and small interfering (si)RNAs, interact with members of the same family of Argonaute (Ago) proteins and their function in target repression is similar, the biogenesis of piRNAs differs from those of the other two small RNAs. Recently, many aspects of piRNA biogenesis have been revealed in Drosophila melanogaster. In this review, we elaborate on piRNA biogenesis in Drosophila somatic and germline cells. We focus on the mechanisms by which piRNA precursor transcription is regulated and highlight recent work that has advanced our understanding of piRNA precursor processing to mature piRNAs. We finish by discussing current models to the still unresolved question of how piRNA precursors are selected and channeled into the processing machinery. The PIWI-interacting RNA (piRNA) pathway is a conserved defense system that protects the genome integrity of the animal germline from deleterious transposable elements. Targets of silencing are recognized by small noncoding piRNAs that are processed from long precursor molecules. Although piRNAs and other classes of small noncoding RNAs, such as miRNAs and small interfering (si)RNAs, interact with members of the same family of Argonaute (Ago) proteins and their function in target repression is similar, the biogenesis of piRNAs differs from those of the other two small RNAs. Recently, many aspects of piRNA biogenesis have been revealed in Drosophila melanogaster. In this review, we elaborate on piRNA biogenesis in Drosophila somatic and germline cells. We focus on the mechanisms by which piRNA precursor transcription is regulated and highlight recent work that has advanced our understanding of piRNA precursor processing to mature piRNAs. We finish by discussing current models to the still unresolved question of how piRNA precursors are selected and channeled into the processing machinery.