CRISPR-Cas adaptive immunity and developments in CRISPR-Cas applications. Reply to comments on "Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems"

Available online at www.sciencedirect.com ScienceDirect Physics of Life Reviews 11 (2014) 149–151 www.elsevier.com/locate/plrev Reply to comments CRISPR–Cas adaptive immunity and developments in CRISPR–Cas applications Reply to comments on “Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems” Edwin L. Cooper ∗ , Nicola Overstreet Laboratory of Comparative Immunology, Department of Neurobiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-1763, United States Received 13 December 2013; accepted 17 December 2013 Available online 21 December 2013 Communicated by M. Frank-Kamenetskii We appreciate the commentaries received from Stern [1], Pinti and Cossarizza [2], Plagens and Randau [3], Koonin [4], Wanner et al. [5], and Severinov [6], and their observations and insights, which we will now discuss. As is mentioned in many of the commentaries received, the emergence of knowledge about CRISPR–Cas systems marks an important shift in the mindset of immunology. For a long time, eukaryotic immune systems were viewed through the paradigm of self/not-self. This paradigm was rooted in clonal selection and the dual innate and adaptive model [7–9]. With the advent of the danger hypothesis, it became apparent that the self/not-self pattern was not im- pervious to upheaval [7,10]. Similarly, small RNA systems have shifted the perspective of immunology. When RNA systems were first discovered, they were seen as an exception to the suite of well-known protein-recognition adaptive immune defenses. However, in the words of Pinti and Cossarizza, “it is now clear even to us, human immunologists, that RNA-based defense mechanisms are the rule, and not the exception, and that the modern, adaptive immune system has been built on an ancient basement made by RNA” [2]. Stern similarly remarks that the wealth of RNA systems reveals the “general solutions to the problem of par- asites” [1]. The recognition of not-self motifs, infected cell death, and retained memory of past exposures are all mechanisms of immune defense that are observed across the tree of life [1]. Koonin likens small RNA defense mech- anisms to an idea that evolution found “ ‘too good’ to be abandoned” [4]. We agree that the pervasiveness of small RNA systems in prokaryotes and eukaryotes demonstrates the importance of these systems to life throughout the phy- logenetic tree, and speaks to the power of these types of systems. As Koonin states, “there seems to be underlying logic in their evolution that is both universal and simple” [4]. DOI of original article: http://dx.doi.org/10.1016/j.plrev.2013.11.002. DOIs of comments: http://dx.doi.org/10.1016/j.plrev.2013.11.004, http://dx.doi.org/10.1016/j.plrev.2013.12.001, http://dx.doi.org/10.1016/j.plrev.2013.11.012, http://dx.doi.org/10.1016/j.plrev.2013.12.002, http://dx.doi.org/10.1016/j.plrev.2013.12.003, http://dx.doi.org/10.1016/j.plrev.2013.11.015. * Corresponding author. 1571-0645/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.plrev.2013.12.011