PIWIL1

PIWIL1, also known as HIWI, is a human gene encoding a member of the PIWI subfamily of Argonaute proteins. The protein product PIWIL1 binds small RNAs called piRNAs (Piwi-interacting RNAs) and is a central component of the piRNA pathway, which protects the genome of animal germ cells from transposable elements.

PIWIL1 participates in transposon silencing and in the regulation of gene expression during germline development. In mammals, piRNA-guided PIWIL1 functions in cytoplasmic silencing of transposon transcripts and, in some developmental stages, in nuclear processes that contribute to de novo DNA methylation and chromatin modification at transposon loci, helping to maintain genomic stability during spermatogenesis.

Its expression is highest in testicular tissue, particularly in developing germ cells, and is also detected in embryonic germ cells and some stem cell populations. Ectopic expression has been reported in certain cancers, where PIWIL1 may be associated with stem cell–like features and disease progression, though its precise role in cancer remains under study.

Structurally, PIWIL1 contains PAZ and PIWI domains characteristic of the PIWI subfamily. The PIWI domain is an RNase H–like endonuclease that can cleave RNA targets in a piRNA-guided manner (slicer activity) in several contexts. PIWIL1 interacts with Tudor-domain proteins, such as members of the TDRD family, and localizes to germline RNA granules, including the chromatoid body, during spermatogenesis.

Genetic studies in model organisms show that PIWIL1 is essential for fertility, with loss of function causing male infertility in mice. In humans, PIWIL1 is the subject of ongoing research regarding its roles in fertility and in cancer biology.