piRNA

piRNA, short for Piwi-interacting RNA, is a class of small non-coding RNAs typically 24 to 31 nucleotides in length that associate with Piwi proteins, a subfamily of Argonaute proteins. Unlike siRNAs and miRNAs, piRNAs are produced through a Dicer-independent pathway and are predominantly expressed in animal germ cells.

The primary function of piRNAs is to silence transposable elements in the genome, thereby protecting genome integrity during gametogenesis. They guide PIWI proteins to transposon transcripts and to chromatin targets, contributing to post-transcriptional silencing as well as transcriptional repression through DNA methylation and repressive histone modifications in many species. This activity reduces transposon mobilization and genomic damage in developing germ cells.

Biogenesis begins with transcription of long single-stranded precursors from genomic piRNA clusters, which are often rich in remnants of transposons. Primary processing involves nucleases such as Zucchini and related factors to produce mature piRNAs that bind PIWI proteins. A secondary amplification loop, known as the ping-pong cycle, generates additional piRNAs with a characteristic 10-nucleotide overlap. In Drosophila, this cycle involves Aubergine and Ago3; in mammals, MILI and MIWI2 participate in related amplification processes. Mature piRNAs commonly undergo 2'-O-methylation at their 3' ends.

Genomic organization of piRNA pathways shows clusters that produce diverse piRNA populations, often reflecting the active transposons in a given tissue or developmental stage. In mammals, MIWI (PIWIL1), MILI (PIWIL2), and MIWI2 (PIWIL4) are key PIWI proteins, with MIWI2 playing a pivotal role in establishing transposon DNA methylation during germ cell development. Disruption of piRNA pathways can impair spermatogenesis and cause germ cell defects or sterility in various species.