PIWIL1

This gene encodes a member of the PIWI subfamily of Argonaute proteins, evolutionarily conserved proteins containing both PAZ and Piwi motifs that play important roles in stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. The encoded protein may play a role as an intrinsic regulator of the self-renewal capacity of germline and hematopoietic stem cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Full Name

piwi-like RNA-mediated gene silencing 1

Function

Endoribonuclease that plays a central role in postnatal germ cells by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. 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 governs the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs. Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Probable component of some RISC complex, which mediates RNA cleavage and translational silencing. Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability. Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1.
Isoform 3
May be a negative developmental regulator (PubMed:12037681, PubMed:16287078).

Biological Process

Gene silencing by RNAISS:UniProtKB
Meiotic cell cycleIEA:UniProtKB-KW
Negative regulation of transpositionISS:UniProtKB
piRNA metabolic processISS:UniProtKB
Regulation of translationIEA:UniProtKB-KW
Spermatid developmentManual Assertion Based On ExperimentIMP:UniProtKB
SpermatogenesisISS:UniProtKB
Spermatogenesis, exchange of chromosomal proteinsISS:UniProtKB

Cellular Location

Cytoplasm
Component of the meiotic nuage, also named P granule, a germ-cell-specific organelle required to repress transposon activity during meiosis. Also present in chromatoid body.

Involvement in disease

Defects in PIWIL1 may be a cause of a disorder resulting in the absence of sperm (azoospermia) in the semen, leading to male infertility. Male sterility can be caused by defects in ubiquitination and degradation during late spermatogenesis.

PTM

Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.
Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in late spermatids, leading to its degradation (PubMed:28552346).
Ubiquitination only takes place following piRNA-binding in adult testis (By similarity).
Ubiquitination and degradation in late spermatogenesis by APC/C is probably required to release RNF8 from the cytoplasm and promote histone to protamine exchange by RNF8 (By similarity).