title: The piRNA Pathway Guards the Germline Genome Against Transposable Elements.
abstract: Transposable elements (TEs) have the capacity to replicate and insert into new genomic locations. This contributs significantly to evolution of genomes, but can also result in DNA breaks and illegitimate recombination, and therefore poses a significant threat to genomic integrity. Excess damage to the germ cell genome results in sterility. A specific RNA silencing pathway, termed the piRNA pathway operates in germ cells of animals to control TE activity. At the core of the piRNA pathway is a ribonucleoprotein complex consisting of a small RNA, called piRNA, and a protein from the PIWI subfamily of Argonaute nucleases. The piRNA pathway relies on the specificity provided by the piRNA sequence to recognize complementary TE targets, while effector functions are provided by the PIWI protein. PIWI-piRNA complexes silence TEs both at the transcriptional level - by attracting repressive chromatin modifications to genomic targets - and at the posttranscriptional level - by cleaving TE transcripts in the cytoplasm. Impairment of the piRNA pathway leads to overexpression of TEs, significantly compromised genome structure and, invariably, germ cell death and sterility.The piRNA pathway is best understood in the fruit fly, Drosophila melanogaster, and in mouse. This Chapter gives an overview of current knowledge on piRNA biogenesis, and mechanistic details of both transcriptional and posttranscriptional TE silencing by the piRNA pathway. It further focuses on the importance of post-translational modifications and subcellular localization of the piRNA machinery. Finally, it provides a brief description of analogous pathways in other systems.
authors.affiliation: Division of Biology and Bioengineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, USA. kft@caltech.edu.
authors.forename: Katalin Fejes
authors.initials: KF
authors.lastname: Tóth
authors.affiliation: Division of Biology and Bioengineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, USA.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Pezic
authors.affiliation: Division of Biology and Bioengineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Stuwe
authors.affiliation: Division of Biology and Bioengineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Webster
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements; D004331:Drosophila melanogaster; D015894:Genome, Human / Q000502:physiology*; D049750:Genome, Insect / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
chemical_list: D004251:DNA Transposable Elements; D034741:RNA, Small Interfering
keywords: Argonautes; DNA methylation; Germ granules; H3K9me3; Heterochromatin; Intramitochondrial cement; Nuage; Pi-bodies; Ping-Pong cycle; Piwi proteins; Pole plasm; Posttranscriptional silencing; Small RNA; TE; Transcriptional silencing; Transposable element; Transposon; Tudor domain; piRNA