PIWIL2
Description
The PIWIL2 (piwi like RNA-mediated gene silencing 2) is a protein-coding gene located on chromosome 8.
PIWIL2, also known as Cancer/testis antigen 80, is a Piwi-like protein 2 that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. It plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells. PIWIL2 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. 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. 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. Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8. When overexpressed, acts as an oncogene by inhibition of apoptosis and promotion of proliferation in tumors (PubMed:16377660). 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). Interacts with DDX4, MAEL, EIF3A, EIF4E, EIF4G, PRMT5 and WDR77 (By similarity). Associates with EIF4E- and EIF4G-containing m7G cap-binding complexes (By similarity). Interacts (when methylated on arginine residues) with TDRD1 and TDRKH/TDRD2 (By similarity). Interacts with TDRD12 (By similarity). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs (By similarity). Interacts with MOV10L1 (By similarity). Interacts with GPAT2 (By similarity). Interacts with TEX19 (By similarity). Interacts with GSK3B (By similarity). Interacts (via PIWI domain) with BMAL1 and CLOCK (PubMed:28903391). Interacts with TEX15 (By similarity).
PIWIL2 is an endoribonuclease that plays a crucial role during spermatogenesis, specifically by repressing transposable elements and preventing their mobilization, which is vital for maintaining germline integrity. It is essential for the meiotic differentiation of spermatocytes, germ cell differentiation, and the self-renewal of spermatogonial stem cells. PIWIL2 operates through the piRNA metabolic process, which involves the formation of complexes composed of piRNAs and Piwi proteins that regulate the methylation and subsequent repression of transposons. During piRNA biosynthesis, PIWIL2 acts as a 'slicer-competent' piRNA endoribonuclease, cleaving primary piRNAs that are then loaded onto 'slicer-incompetent' PIWIL4. This slicing produces a pre-miRNA intermediate, which is further processed into mature piRNAs, along with a 16-nucleotide by-product that is degraded. PIWIL2 is necessary for the nuclear localization of PIWIL4/MIWI2 and its association with secondary piRNAs antisense. Beyond their role in repressing transposable elements, piRNAs are likely involved in other processes during meiosis, such as translation regulation. PIWIL2 indirectly modulates the expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9, and STRA8. When overexpressed, it acts as an oncogene by inhibiting apoptosis and promoting proliferation in tumors. PIWIL2 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.
PIWIL2 is also known as CT80, HILI, PIWIL1L, mili.
Associated Diseases
- partial chromosome Y deletion
- male infertility with teratozoospermia due to single gene mutation
- spermatogenic failures 50
- spermatogenic failure 25
- spermatogenic failure, X-linked, 2
- spermatogenic failure 61
- spermatogenic failure 74
- spermatogenic failure 73
- spermatogenic failure 48
- spermatogenic failure 63
- spermatogenic failure 22
- spermatogenic failure, X-linked, 3
- spermatogenic failure 40
- spermatogenic failure 70
- spermatogenic failure 65
- spermatogenic failure 72
- spermatogenic failure 39
- spermatogenic failure 47
