Fig. 1

Overview of the PIWI-piRNA pathway. a Structures of the fruitfly Piwi and silkworm Siwi [2, 3]. Piwi and Siwi are highly conserved and shared eight regions that form four common domains. The N-terminal domain, PAZ domain, MID domain, and PIWI domain and interspersed by L0, L1, and L2 sequences. The nuclear localization signal (NLS) in the N domain of Piwi enables the nuclear localization. Siwi does not contain an NLS and is a cytoplasmic protein. b The first 3D structure of a Piwi protein-Siwi by Matsumoto et al. [2]. Siwi is divided into two lobes. L0, N, L1, PAZ, and L2 domains form the N-PAZ lobe, whereas L0, L2, MID, and PIWI domains form the MID-PIWI lobe. These two lobes give rise to a nucleic acid-binding channel. c Biogenesis of piRNAs in Drosophila. piRNA precursor is transcribed from piRNA clusters and exported from nucleus. 5′ end monophosphorylated piRNA precursors are bond by Piwi protein loaded with initiator piRNAs and processed into pre-piRNA and pre-pre-piRNA. Pre-pre-piRNAs are phased by Zucchini endonuclease (Zuc) [4,5,6] while pre-piRNAs are trimmed by Nibbler to produce mature piRNAs [7, 8]. Finally, the 3′ end of piRNAs are 2′O-methylated by the Hen1 methylase [9,10,11,12]. After 2-O-methylation, the mature piRNA-Piwi complex further initiates ping-pong piRNA biogenesis facilitated by the other two Piwi proteins Ago3 and Aub [13, 14]. d Biogenesis of piRNAs in C. elegans [15]. piRNA precursors in C. elegans are short RNAs with a length of 25–27 nt. The processed piRNA precursors were also trimmed and 2′O-methylated by respective nucleases to generate mature piRNAs. e Prevalent models for Piwi-mediated transcriptional silencing of transposons. In the nucleus of fruitfly (upper panel), the Piwi-piRNA complex binds to a nascent transposon transcript and recruits Panoramix (Panx) and Asterix (Arx) mediator complex to the vicinity of the target chromatin region. Panoramix further interacts with Nxf2 and Nxt1 and which recruits histone methytransferase, dSetDB1(dSET) to methylate the Lysine residue at the 9th position of histone 3, which establishes a repressive chromatin state to suppress transposon expression [16,17,18,19,20,21,22]. In mice (lower panel), piRNA-loaded MIWI2 associates with TDRD9, DNMT3L, DNMT3a, and DNMT3a2 in transfected 293 T cells. The complex is guided by piRNA and deposits DNA methylation via DNMT3a2 [23]. However, the latest reports indicated that SPOCD1 links MIWI2 to Dnmt3a and Dnmat3L and the complex also contain TEX15 [24, 25]. Therefore, how exactly these proteins interact with each other remain unknown