Guest list or black list: heritable small RNAs as immunogenic memories

Abstract

Small RNA-mediated gene silencing plays a pivotal role in genome immunity by recognizing and eliminating viruses and transposons which otherwise may colonize the genome. However, this can be challenging since individual genomic parasites are highly diverse, and employ multiple immune evasion techniques. In this review, I discuss a new theory proposing that the integrity of the germline is maintained by transgenerationally-transmitted RNA "memories" that record ancestral gene expression patterns, and delineate "Self" from "Foreign" sequences. To maintain such recollection two tactics are employed in parallel: "black listing" of invading nucleic acids, and "guest listing" of endogenous genes. Studies in a number of organisms have shown that this memorization is used by the next generation small RNAs to act as "Inherited Vaccines" that ambush invading elements, or as "Inherited Licenses" that grant the transcription of autogenous sequences. KeywordsSmall RNA; Transgenerational Inheritance; Inherited Immunity; Self Vs. Non-Self; "Inherited Vaccines" Overview of transgenerational inheritanceEvolution progresses through an interplay between two major forces, selection and variation. Since the formulation of the Modern Synthesis the theory holds that the environment is limited in its contribution to the evolutionary course of action -it affects selection, but not the degree of variation [1,2]. However, recent discoveries in epigenetics suggest that the environment may influence variability as well [1]. If the parental environment is predictive of the conditions that the progeny will face (often for sessile or short-lived organisms), epigenetic responses can change the output of the encoded genetic information in an adaptive manner [3]. For example, the water flea Daphnia changes its normal developmental course and develops a "helmet" that protects it from predators, if it is born to a mother that survived a similar attack [4].Correspondence to: odedrechavi@gmail.com. Over the years, controversy surrounded the study of environmentally affected transgenerational inheritance. Today, an improved understanding of epigenetic mechanisms at the molecular level has provided a logical background to explain how, heretically, an adaptive acquired trait could become heritable [5]. Several epigenetic mechanisms could regulate the expression of relevant genes during transgenerational inheritance including DNA methylation, histone modification, and transmission of regulatory RNAs. Moreover, in many organisms, these pathways appear to be interconnected [5][6][7][8]. Europe PMC Funders GroupThis review will concentrate on recent discoveries that establish a role for small RNAs in transgenerational transmission of acquired defense. Furthermore, exciting examples of RNA-mediated non-Mendelian genetic effects will be discussed, along with their possible implications for the study of evolution and immunology. RNA-mediated gene silencing and inheritanceSince the original discovery that small RNAs derived from exogenously-provided dou...

Biosafety by definition: an analysis of the New Zealand Environmental Protection Authority’s reasons for not classifying organisms treated with double-stranded RNA as genetically modified or new organisms

“…As discussed 572 above, that is a kind of modification that can result from a treatment with exo-dsRNAs 573 without reliance on continued transcription (Rechavi, 2014 Likewise, EPA could have reduced compliance costs for those using exo-dsRNA in contained 596 facilities by limiting the approval to synthetically produced dsRNA molecules, as requested 597 in the original application, prohibiting dsRNA derived from pathogens such as RNA viruses. 598…”

Épigénétique et réponses transgénérationnelles aux impacts de l’environnement

“…Quelles sont les fenêtres de sensibilité, d'insensibilité à ces facteurs ? Comment les différences liées au sexe des parents imposent-elles un dimorphisme sexuel sur la progéniture voire les générations suivantes [3,12,26,29,56] ? L'implication de l'épigénétique dans les effets/réponses inter/transgénérationnels manque encore d'un modèle fédérateur [29].…”

Why are individuals so different from each other?

“…In the plant Arabidopsis, epigenetic inheritance can occur over at least eight generations (Johannes et al, 2009;Cortijo et al, 2014). In the nematode worm Caenorhabditis elegans, stable transmission across generations depends on gene regulation by microRNA (Rechavi, 2014). Rassoulzadegan (2011) found that injection of RNA from sperm from one strain of mice into wild-type embryos led to a distinct phenotype in the offspring, which was in turn transmitted to their progeny.…”