Small silencing RNA Biology and Mechanism
Séminaire FSER organisé par Philip Zamore (University of Massachusetts) et Christophe Antoniewski (Université Pierre et Marie Curie, Paris) du 23 au 28 avril 2012
Christophe Antoniewski, Julius Brennecke, Jérôme Cavaillé, Helge Groshans, René Ketting, Eric C. Lai, Ruth Lehmann, Allison Mallory, Danesh Moazed, Alain Pélisson, Ramesh Pillai, Carla Saleh, Hervé Seitz, Martine Simonelig, Mikiko Siomi, William Theurkauf, Yukihide Tomari, Olivier Voinnet, Phillip Zamore
Fifteen to 30 nucleotide-long RNAs lie at the core of a vast silencing network in animals and plants. These small silencing RNAs bind to a member of the Argonaute family of proteins to form RNA-induced silencing complexes (RISC), which they guide to complementary targets. Small RNA-directed silencing may occur by cleavage, destabilization or inhibition of translation of RNA transcripts, or by DNA or histone modification at complementary loci. Small RNAs regulate many essential biological processes, from cell differentiation and reprogramming to defense against exogenous pathogens and endogenous transposons, and even modulate chromatin dynamics.
The meeting gathered 19 scientists in the opulent and collegial environment of Les Treilles estate to discuss recent developments in understanding the biogenesis, mechanisms of action and function of the three major classes of small RNAs: microRNAs (miRNAs), small interfering RNAs (siRNAs), and Piwi-interacting RNAs (piRNAs).
Yukihide Tomari (University of Tokyo, Japan) showed that the RNase III enzyme Dcr-2, its partner R2D2, and five chaperone proteins are sufficient for Ago2-RISC assembly in flies. These components consume ATP, and he proposed that the ATP is used to stretch RISC, allowing it to accommodate small RNA duplexes. In his model, release of the “tension” inherent in the process subsequently helps to disgorge the passenger strand. Yukihide also showed that microRNAs mediate gene silencing via multiple parallel pathways in Drosophila, some of which may be conserved in plants.
In plants, a process called RNA quality control (RQC) leads to RNA decay, thereby ensuring that error bearing RNAs are eliminated. Allison Mallory (INRA, Versailles, France) showed that several RQC components antagonize siRNA-direct post-transcriptional gene silencing (PTGS) in Arabidopsis thaliana. Indeed, the XRNs, exosome complexes, and components of the decapping, deadenylation and nonsense mediated decay complexes are endogenous suppressors of PTGS. She reported that many of the RNA turnover and RQC factors affecting PTGS localize in two dynamically linked cytoplasmic RNA degradation foci: siRNA-bodies and processing (P) -bodies, although compartmentalization in the nucleus was also observed. These findings suggest cross-regulations between RNA turnover, RQC and PTGS pathways.
Olivier Voinnet (ETH-Z, Zurich, Switzerland) described a genetic strategy to reactivate one of the few intact transposons present in Arabidopsis thaliana, the retroelement EVADE (EVD). Olivier showed that the cell initially perceives EVD as an RNA virus, so EVD has developed a silencing suppression strategy that counteracts the plants PTGS defenses, allowing EVD to proliferate over the generations.