PiRNA-Guided CRISPR-like Immunity in Eukaryotes. Issue 11 (November 2019)

• Record Type: Journal Article
• Authors: Ophinni, Youdiil; Palatini, Umberto; Hayashi, Yoshitake; Parrish, Nicholas F.
• Is Part Of: Trends in immunology. Volume 40:Issue 11(2019)
• Page Start: 998
• Page End: 1010
• Publication Date: 2019-11
• Subjects: piRNA -- Piwi protein -- endogenous viral elements -- transposable elements -- RNAi; Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2019.09.003
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Eukaryotic genomes contain virus-derived sequences called endogenous virus elements (EVEs). The majority of EVEs are related to retroviruses, which integrate into the host genome in order to replicate. Some retroviral EVEs encode a function; for example, some produce proteins that block infection by related viruses. EVEs derived from nonretroviral viruses – also recently found in many eukaryotic genomes – are more enigmatic. Here, we summarize the evidence that EVEs can act as templates to generate Piwi-interacting RNAs (piRNAs), whose canonical function is sequence-specific silencing of transposable elements (TEs) to maintain genomic integrity. We argue that EVEs may thus enable heritable, sequence-specific antiviral immune memory in eukaryotes – analogous to CRISPR-Cas immunity in prokaryotes. Highlights: Virus-derived sequences called endogenous viral elements (EVEs) are present and sometimes abundant in eukaryotic genomes. EVEs can even be derived from viruses that do not encode the enzymes needed to integrate into their host's genome. Piwi-interacting RNAs (piRNAs) are made from some EVEs. In some species, EVEs are enriched in piRNA-generating regions of the genome, called piRNA clusters. piRNAs interact with Piwi proteins, abundant in the gonads of model organisms and humans. RNAs transcribed from piRNA clusters have been found in somatic cells, but it is unknown if these interact with Piwi proteins. Canonically, Piwi–piRNA complexes silence transposable elements (TEs) by RNAi. However, not all piRNAs target TEs, and the function of these piRNAs is unclear. New evidence is consistent with antiviral RNAi activity of EVE-derived piRNAs in a number of invertebrates and vertebrates, including mammals; we argue that piRNAs may guide transgenerational sequence-specific adaptive immunity, similar to CRISPR RNAs in prokaryotes.