Revisão Revisado por pares

piRNA-Guided CRISPR-like Immunity in Eukaryotes

2019; Elsevier BV; Volume: 40; Issue: 11 Linguagem: Inglês

10.1016/j.it.2019.09.003

ISSN

1471-4981

Autores

Youdiil Ophinni, Umberto Palatini, Yoshitake Hayashi, Nicholas F. Parrish,

Tópico(s)

RNA and protein synthesis mechanisms

Resumo

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. 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. 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. produced from EVEs generated by germline insertion of viral nucleic acid sequence information, these represent sequence-specific memory of previous viral infection. RNAi mediated by anamnestic piRISCs. molecules or programs that inhibit viral replication or virus-induced pathology. We include as viruses the Metaviridae and other Ortervirales members that – while capable of producing cell-to-cell infectious particles – are also considered TEs. family of proteins that bind to small noncoding RNAs and silence complementary target RNAs. Contain at least two domains: Piwi–Argonaute–Zwille (PAZ, the RNA-binding module) and PIWI (RNaseH-like target cleaving module). germline-integrated fragments of ancient Bornaviridae family members found within many mammalian genomes. Originated from viral transcript reverse transcription and integration of ancient bornaviral mRNA. virus-derived sequences found within eukaryotic host genomes, these represent one form of HGT. Can be complete viral genomes or fragments thereof. EVEs of retrovirus-like sequences found within eukaryotic genomes, constituting metaviruses as well as sequences derived from of exogenous β-, δ-, γ- and spuma-retroviruses that have integrated into the germline. a genera of LTR-type RT-encoding TEs – also classified as viruses belonging to the Metaviridae family – present in many eukaryotic genomes. In some cases, these are also capable of infecting in a cell-to-cell manner, for example gypsy encoded by D. melanogaster. movement of genetic material between organisms horizontally, that is, other than from parent to progeny. piRNAs that guide PIWI proteins to cleave long piRNA precursors at the 5′ end, creating pre-pre-piRNAs that further produce responder or trailing piRNAs. EVEs derived from viruses that are not retroviruses. RNA-binding Argonaute proteins conserved among eukaryotes containing PAZ, MID, and PIWI domains; defined as a family based on phylogenetic clustering. genomic region that gives rise to piRNAs, thought to act as genetic traps; that is, any mobile genetic elements entering these loci can be recognized and subsequently silenced. a disputed term without standardized meaning and thus potentially harmful; arbitrarily applied to small RNAs with some characteristics often associated with piRNAs; for example, size or cluster mapping, but for which interaction with Piwi proteins is not established. RNAs that specifically interact with Piwi proteins. The most abundantly expressed small noncoding RNAs present in animal germline cells. Approximately 24–31 nt in length, their biogenesis is Piwi-dependent, and canonically guides Piwi protein to enact TE silencing in the germline. complex including an Argonaute protein bound to a small RNA forming a ribonucleoprotein capable of silencing target RNAs. silencing of target RNAs with complementarity to small RNAs 20–35 nt in length (siRNAs, miRNAs, and piRNAs); a key process in genomic regulation and defense against foreign genetic elements. inherited mechanism to differentiate nonself viruses from self, preventing harm to the host. Well studied in prokaryotes (CRISPR-Cas) but poorly understood in eukaryotes. DNA sequences that can change their position within a genome; once considered junk DNA, there has been a shift to ascribe to them functions, or as described by Barbara McClintock, controlling elements. process in which a viral mRNA interacts with an RT, presumably host-encoded, and is thereby converted from RNA to DNA. proposed by August Weismann; it is a theoretical boundary preventing passage of genetic information from somatic cells to germline cells, from which it could be inherited by the next generation. Called Biology's Second Law, it underlies the rejection of Lamarckianism and the conceptual dichotomy between endogenous and exogenous viruses.

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