Piwil2
Developmental stage
Expressed from 12.5 dpc until adult in male gonads. In female gonads, detected since 12.5 dpc, then begins to cease after birth and disappears until the development of adult ovary (PubMed:11578866). Highly expressed in embryonic male germ cells at embryonic day 16.5 and expression decreases by postnatal day 2.5 (PubMed:32381626).
Function
Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4 (PubMed:22020280, PubMed:23706823, PubMed:26669262). PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded (PubMed:28633017). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (PubMed:18381894, PubMed:18922463, PubMed:26669262). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:19114715). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (PubMed:16261612). Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK by inhibiting GSK3B-mediated phosphorylation and ubiquitination-dependent degradation of these proteins (PubMed:28903391).
Post-translational modifications
Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein TDRD1 and subsequent localization to the meiotic nuage, also named P granule.
Sequence Similarities
Belongs to the argonaute family. Piwi subfamily.
Tissue Specificity
Expressed in adult testis, specifically in spermatocytes and in spermatogonia (PubMed:11279525, PubMed:11578866, PubMed:12906857, PubMed:18404146, PubMed:18922463, PubMed:19114715, PubMed:19377467, PubMed:28903391). Only detected in primordial germ cells of both sexes. Widely expressed in tumors. Also present at early stages of oocyte growth. Present in the mitotic spermatogonia (PubMed:23706823). Not detected in the first stages of meiosis (preleptotene and leptotene) (PubMed:23706823). Detected at the late zygotene stage and increases throughout pachytene, declining from this stage onward until expression stops at the early round spermatid stage (at protein level) (PubMed:23706823).
Cellular localization
- Cytoplasm
- Present in chromatoid body. Probable component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis (PubMed:20439430).
Alternative names
Mili, Piwi-like protein 2