The rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans

Abstract

Double-stranded (ds) RNA can induce sequence-specific inhibition of gene function in several organisms. However, both the mechanism and the physiological role of the interference process remain mysterious. In order to study the interference process, we have selected C. elegans mutants resistant to dsRNA-mediated interference (RNAi). Two loci, rde-1 and rde-4, are defined by mutants strongly resistant to RNAi but with no obvious defects in growth or development. We show that rde-1 is a member of the piwi/sting/argonaute/zwille/eIF2C gene family conserved from plants to vertebrates. Interestingly, several, but not all, RNAi-deficient strains exhibit mobilization of the endogenous transposons. We discuss implications for the mechanism of RNAi and the possibility that one natural function of RNAi is transposon silencing.

RNA interference: The molecular immune system

“…In these species siR-NA signals are readily transmitted from cell to cell, although the mechanisms of heritability and intracellular communication underlying these observations are not yet explained (Figure 1. Fire 1999, Hamilton & Baulcombe 1999, Ketting et al 1999, Sharp 1999, Tabara et al 1999, Tuschl 1999, Bass 2000, Zamore et al 2000, Grishok & Mello 2002, Hannon 2002, Hutvagner & Zamore 2002, Lindenbach & Rice 2002, Salo et al 2002, Urwin et al 2002. A model for the mechanism of mRNA degradation by RNAi.…”

“…RNAi, miRNA, tncRNA, molecular immunity, homology-dependent gene silencing, and DNA dependent methylation are host defenses that rely on homologous host-retroelement gene sequences (Bagasra 1999, Fire 1999, Hamilton & Baulcombe 1999, Ketting et al 1999, Sharp 1999, Tabara et al 1999, Tuschl 1999, Bass 2000, Zamore et al 2000, Grishok & Mello 2002, Hannon 2002, Hutvagner & Zamore 2002, Lindenbach & Rice 2002, Salo et al 2002, Urwin et al 2002. These defenses have evolved to accommodate both the host and the parasite (Bagasra & Amjad 1997, Bagasra 1999, Fire 1999, Hamilton & Baulcombe 1999, Ketting et al 1999, Sharp 1999, Tabara et al 1999, Tuschl 1999 Seitz et al 2003).…”

“…The concept of ''molecular immunity'' results from a fusion of concepts from diverse fields including plant biology, molecular genetics, immunology, and biochemistry; they have contributed to describing a mechanism by which eukaryotes are able to regulate gene expression, fight double-stranded RNA (dsRNA) viral infections, and protect their genomes from genetic parasites such as transposons (the DNA mobile elements that move from one location to another), retrotransposons (the DNA mobile element that use RNA intermediate), and retroviruses (Fire 1999, Hamilton & Baulcombe 1999, Ketting et al 1999, Sharp 1999, Tabara et al 1999, Tuschl 1999, Bass 2000, Zamore et al 2000, Grishok & Mello 2002, Hannon 2002, Hutvagner & Zamore 2002, Lindenbach & Rice 2002, Salo et al 2002, Urwin et al 2002, Seitz et al 2003. In the last several years, numerous examples of RNAbased intracellular molecular defense mechanisms have been described.…”

“…Here we will review some of the recent work concerning RBGS and present a novel hypothesis that includes possible alternate mechanisms which may function in vivo to mediate immunity associated with the control of retroelements and transposons (Bagasra 1999, Ketting et al 1999, Tabara et al 1999. We shall also offer some thoughts on the significance of these mechanisms from an evolutionary perspective.…”

Gene silencing: Double-stranded RNA mediated mRNA degradation and gene inactivation

“…Aberrant RNAs that are misspliced and polyadenylated irregularly have been detected in a chalcone synthase PTGS system in petunia [37]. A new aspect of ego1 C. elegans Smardon et al 2000 [12] eIF2C-like qde2 Neurospora Catalanotto et al 2000 [42] Rde1 C. elegans Tabara et al 1999 [43] ago1 Arabidopsis Fagard et al 2000 [20] RecQ DNA qde3 Neurospora Cogoni et al 1999 [44] RNase D-like mut-7 C. elegans Ketting et al 1999 [45] RNA helicase mut-6 Chlamydomonas Wu-Scharf et al 2000 [33] Coiled-coil Protein Sgs3 Arabidopsis Mourrain et al 2000 [21] NMD Proteins smg2,5,6 C. elegans Domeier et al 2000 [46] rgs-CaM No Nicotiana tabacum Domeier et al 2000 [46] ago1 argonaute1; ego1, enhancer of glp-1; qde, quelling defective; rde, RNA interference deficient; rgr-CaM, regulator of gene silencing calmodulin-like protein; sde, silencing defective; sgs, suppressor of gene silencing silencing processes is the possible link with nonsense-mediated decay (NMD), an evolutionarily conserved pathway in which mRNAs that contain a premature stop codon are selectively degraded. Antisense constructs probably also produce RNAs that feed into the dsRNA-induced degradation pathway [38], [39].…”