Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity

Abstract

Highlights d circRNAs are globally degraded by activated RNase L upon viral infection d Many circRNAs tend to form 16-26 bp duplexes and act as endogenous PKR inhibitors d The RNase L-mediated circRNA degradation is required for PKR activation d circRNA reduction and aberrant PKR activation are found in autoimmune disease SLE

Past, present, and future of circ RNA s

“…The EMBO Journal 38: e100836 | 2019 blood mononuclear cells derived from systemic lupus erythematosus patients (Liu et al, 2019). In addition to degradation, circRNAs might be eliminated from cells by exocytosis.…”

“…The EMBO Journal 38: e100836 | 2019 ª 2019 The Authors (Liu et al, 2019). These hairpins are bound by RBPs responsible for intracellular immune response.…”

“…A subset of circRNA produces proteins in the fly brain and in murine and human cells Pamudurti et al, 2017;Yang et al, 2017), and others seem to be related to the immune response (Li et al, 2017a;Liu et al, 2019). A subset of circRNA produces proteins in the fly brain and in murine and human cells Pamudurti et al, 2017;Yang et al, 2017), and others seem to be related to the immune response (Li et al, 2017a;Liu et al, 2019).…”

Circle the Wagons: Circular RNAs Control Innate Immunity

“…PKR thus needs to be readily activatable yet maintained in an inactive state in uninfected cells to prevent inappropriate reactions and autoimmunity. Previous work has shown that PKR activation can be blocked upon binding the adenovirus small noncoding VAI RNA (Kitajewski et al, 1986) or short (16-33 bp) dsRNAs (Zheng and Bevilacqua, 2004), and Liu et al (2019) now find that many endogenous circular RNAs are able to bind PKR. Interestingly, when the binding profiles of linear and circular RNAs of the same sequence were compared, circular RNAs bound much more strongly to PKR.…”

“…Most other individual circular RNAs are expressed at exceedingly low levels, so it has remained unclear what biological function (if any) they exert. In this issue of Cell, Liu et al (2019) reveal that circular RNAs can collectively bind and suppress activation of the kinase PKR, thereby controlling innate immune responses. The innate immune system is the first line of defense against invading pathogens and involves a set of receptors that recognize pathogen structures (reviewed in Mogensen, 2009).…”