PIWIL4
Description
The PIWIL4 (piwi like RNA-mediated gene silencing 4) is a protein-coding gene located on chromosome 11.
PIWIL4, also known as Piwi-like protein 4, is a protein that in humans is encoded by the PIWIL4 gene. It is a member of the PIWI protein family, which is characterized by a PAZ domain and a PIWI domain. PIWIL4 is involved in the piRNA pathway, which is a mechanism for silencing transposable elements in the germline. It is essential for spermatogenesis and plays a role in the regulation of somatic cells activities, including pancreatic beta cell function and insulin secretion.
PIWIL4 is involved in the piRNA metabolic process, which silences transposable elements during meiosis. It forms complexes with piRNAs and other Piwi proteins, ultimately leading to the methylation and suppression of transposons. PIWIL4 binds directly to piRNAs, a unique class of small RNAs generated independently of the Dicer enzyme. These piRNAs primarily originate from transposons and other repetitive DNA sequences. PIWIL4 interacts with PIWIL2/MILI and is essential for the association with secondary piRNAs antisense. The piRNA pathway acts upstream of known DNA methylation regulators. Notably, PIWIL4 lacks endonuclease activity. It plays a crucial role in the piRNA amplification loop, also known as the ping-pong amplification cycle. Acting as a 'slicer-incompetent' component, it loads cleaved piRNAs from the 'slicer-competent' PIWIL2, targeting them to transposon loci within the nucleus. PIWIL4 may participate in chromatin modifications, inducing methylation of histone H3 at lysine 9 (H3K9me) at specific loci. Beyond its germline functions, PIWIL4 also regulates somatic cell activities. It contributes to pancreatic beta cell function and insulin secretion. PIWIL4 is involved in maintaining the morphology and functionality of retinal epithelial cells through the Akt/GSK3alpha/beta signaling pathway. Overexpression of PIWIL4 can act as an oncogene, inhibiting apoptosis and promoting cell proliferation in tumors.
PIWIL4 is also known as HIWI2, MIWI2.
Associated Diseases
- cancer
- male infertility with teratozoospermia due to single gene mutation
- partial chromosome Y deletion
- spermatogenic failure, X-linked, 2
- spermatogenic failures 50
- isolated congenital hypogonadotropic hypogonadism
- spermatogenic failure 25
- congenital bilateral absence of vas deferens
- 46,XX testicular disorder of sex development
- isochromosomy Yp
- spermatogenic failure 63
- spinocerebellar ataxia type 32
- spermatogenic failure 72
- spermatogenic failure 48
