Genomes and Genes
Gene Symbol: r2d2
Alias: CG7138, Dmel\CG7138, R2D2, R2d2, cg7138, r2d2, CG7138-PA, CG7138-PB, CG7138-PC, R2D2, r2d2-PA, r2d2-PB, r2d2-PC
Species: fruit fly
- Obbard D, Jiggins F, Halligan D, Little T. Natural selection drives extremely rapid evolution in antiviral RNAi genes. Curr Biol. 2006;16:580-5 pubmed..that the rate of amino acid evolution is substantially elevated in genes related to antiviral RNAi function (Dcr2, R2D2, and Ago2)...
- He L, Hannon G. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522-31 pubmed
- Cenik E, Fukunaga R, Lu G, Dutcher R, Wang Y, Tanaka Hall T, et al. Phosphate and R2D2 restrict the substrate specificity of Dicer-2, an ATP-driven ribonuclease. Mol Cell. 2011;42:172-84 pubmed publisher..purified Dicer-2 can efficiently cleave pre-miRNA, but that inorganic phosphate and the Dicer-2 partner protein R2D2 inhibit pre-miRNA cleavage...
- Marques J, Kim K, Wu P, Alleyne T, Jafari N, Carthew R. Loqs and R2D2 act sequentially in the siRNA pathway in Drosophila. Nat Struct Mol Biol. 2010;17:24-30 pubmed publisher..This pathway requires Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) called R2D2. A potentially distinct siRNA pathway, which requires Dcr-2 in association with a different dsRBP, called ..
- Nishida K, Miyoshi K, Ogino A, Miyoshi T, Siomi H, Siomi M. Roles of R2D2, a cytoplasmic D2 body component, in the endogenous siRNA pathway in Drosophila. Mol Cell. 2013;49:680-91 pubmed publisher..interfering RNAs (endo-siRNAs) in Drosophila are processed by Dicer-2 (Dcr-2) and loaded onto Ago2 by the Dcr-2/R2D2 heterodimer. In r2d2 mutants, the level of endo-siRNAs is unchanged, but endo-siRNAs are misloaded onto Ago1...
- Lim D, Kim J, Kim S, Carthew R, Lee Y. Functional analysis of dicer-2 missense mutations in the siRNA pathway of Drosophila. Biochem Biophys Res Commun. 2008;371:525-30 pubmed publisher..It also interacts with the siRNA product and R2D2 protein to facilitate the assembly of an RNA-induced silencing complex (RISC) that mediates RNA interference...
- Jiang F, Ye X, Liu X, Fincher L, McKearin D, Liu Q. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev. 2005;19:1674-9 pubmedIn Drosophila melanogaster, Dicer-2/R2D2 and Dicer-1 generate small interfering RNA (siRNA) and microRNA (miRNA), respectively...
- Hammond S. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett. 2005;579:5822-9 pubmed..Silencing is effected by the RNA-induced silencing complex and its RNaseH core enzyme Argonaute. This review describes the discovery of these machines and discusses future lines of work on this amazing biochemical pathway. ..
- Chung W, Okamura K, Martin R, Lai E. Endogenous RNA interference provides a somatic defense against Drosophila transposons. Curr Biol. 2008;18:795-802 pubmed publisher..Drosophila utilizes two small-RNA systems to restrict transposon activity in the germline (mostly via piRNAs) and in the soma (mostly via siRNAs). ..
- Liu X, Park J, Jiang F, Liu Y, McKearin D, Liu Q. Dicer-1, but not Loquacious, is critical for assembly of miRNA-induced silencing complexes. RNA. 2007;13:2324-9 pubmedDouble-stranded RNA-binding proteins (dsRBPs), such as R2D2 and Loquacious (Loqs), function in tandem with Dicer (Dcr) enzymes in RNA interference (RNAi)...
- Okamura K, Chung W, Ruby J, Guo H, Bartel D, Lai E. The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature. 2008;453:803-6 pubmed publisher..These novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biological usage of endogenous RNA interference in Drosophila. ..
- Pham J, Pellino J, Lee Y, Carthew R, Sontheimer E. A Dicer-2-dependent 80s complex cleaves targeted mRNAs during RNAi in Drosophila. Cell. 2004;117:83-94 pubmed..Dcr-2 does not simply transfer siRNAs to a distinct effector complex, but rather assembles into RISC along with the siRNAs, indicating that its role extends beyond the initiation phase of RNAi. ..
- Tomari Y, Zamore P. MicroRNA biogenesis: drosha can't cut it without a partner. Curr Biol. 2005;15:R61-4 pubmed
- Forstemann K, Horwich M, Wee L, Tomari Y, Zamore P. Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by dicer-1. Cell. 2007;130:287-97 pubmed..Thus, the two members of the Drosophila Ago subclade of Argonaute proteins are functionally specialized, but specific small RNA classes are not restricted to associate with Ago1 or Ago2. ..
- Tomari Y, Zamore P. Perspective: machines for RNAi. Genes Dev. 2005;19:517-29 pubmed..Here, we review our current understanding of how small RNAs are produced, how they are loaded into protein complexes, and how they repress gene expression. ..
- Vagin V, Sigova A, Li C, Seitz H, Gvozdev V, Zamore P. A distinct small RNA pathway silences selfish genetic elements in the germline. Science. 2006;313:320-4 pubmed..Our data suggest that rasiRNAs protect the fly germline through a silencing mechanism distinct from both the miRNA and RNA interference pathways. ..
- Liu Q, Rand T, Kalidas S, Du F, Kim H, Smith D, et al. R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science. 2003;301:1921-5 pubmed..S2cells and consists of two stoichiometric subunits: Dicer-2(DCR-2) and a previously unknown protein that we named R2D2. R2D2 is homologous to the Caenorhabditis elegans RNAi protein RDE-4...
- Mueller S, Gausson V, Vodovar N, Deddouche S, Troxler L, Perot J, et al. RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila. Proc Natl Acad Sci U S A. 2010;107:19390-5 pubmed publisher..This result is of particular interest in view of the frequent transmission of medically relevant negative-strand RNA viruses to humans by insect vectors. ..
- Saito K, Ishizuka A, Siomi H, Siomi M. Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol. 2005;3:e235 pubmed..These results support a model in which Loquacious mediates miRNA biogenesis and, thereby, the expression of genes regulated by miRNAs. ..
- Deddouche S, Matt N, Budd A, Mueller S, Kemp C, Galiana Arnoux D, et al. The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila. Nat Immunol. 2008;9:1425-32 pubmed publisher..We propose that this family represents an evolutionary conserved set of sensors that detect viral nucleic acids and direct antiviral responses. ..
- Kavi H, Fernandez H, Xie W, Birchler J. RNA silencing in Drosophila. FEBS Lett. 2005;579:5940-9 pubmed..RNA silencing processes in Drosophila are described. ..
- Forstemann K, Tomari Y, Du T, Vagin V, Denli A, Bratu D, et al. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 2005;3:e236 pubmed..Thus, every known Drosophila RNase-III endonuclease is paired with a dsRBD protein that facilitates its function in small RNA biogenesis. ..
- Okamura K, Balla S, Martin R, Liu N, Lai E. Two distinct mechanisms generate endogenous siRNAs from bidirectional transcription in Drosophila melanogaster. Nat Struct Mol Biol. 2008;15:581-90 pubmed publisher..These newly recognized siRNA pathways broaden the scope of regulatory networks mediated by small RNAs. ..
- Tomari Y, Du T, Zamore P. Sorting of Drosophila small silencing RNAs. Cell. 2007;130:299-308 pubmed..We find that the Dcr-2/R2D2 heterodimer acts as a gatekeeper for the assembly of Ago2 complexes, promoting the incorporation of siRNAs and ..
- Tomari Y, Matranga C, Haley B, Martinez N, Zamore P. A protein sensor for siRNA asymmetry. Science. 2004;306:1377-80 pubmed..We show that in Drosophila, the orientation of the Dicer-2/R2D2 protein heterodimer on the siRNA duplex determines which siRNA strand associates with the core RISC protein ..
- Hartig J, Forstemann K. Loqs-PD and R2D2 define independent pathways for RISC generation in Drosophila. Nucleic Acids Res. 2011;39:3836-51 pubmed publisher..Endo- and exo-siRNAs display a differential requirement for double-stranded RNA binding domain proteins (dsRBPs): R2D2 is needed to load exo-siRNAs into Ago2 while the PD isoform of Loquacious (Loqs-PD) stimulates Dcr-2 during the ..
- Ghildiyal M, Xu J, Seitz H, Weng Z, Zamore P. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA. 2010;16:43-56 pubmed publisher..Central to this sorting decision is the affinity of the small RNA duplex for the Dcr-2/R2D2 heterodimer, which loads small RNAs into Ago2...
- Matranga C, Tomari Y, Shin C, Bartel D, Zamore P. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell. 2005;123:607-20 pubmed..For siRNAs, virtually all RISC is assembled through this cleavage-assisted mechanism. In contrast, passenger-strand cleavage is not important for the incorporation of miRNAs that derive from mismatched duplexes. ..
- Miyoshi K, Miyoshi T, Hartig J, Siomi H, Siomi M. Molecular mechanisms that funnel RNA precursors into endogenous small-interfering RNA and microRNA biogenesis pathways in Drosophila. RNA. 2010;16:506-15 pubmed publisher..The Dicer2-Loqs-PD complex contains R2D2, another known Dicer2 partner, and excises both exogenous siRNAs and esiRNAs from their corresponding precursors in ..
- Okamura K, Robine N, Liu Y, Liu Q, Lai E. R2D2 organizes small regulatory RNA pathways in Drosophila. Mol Cell Biol. 2011;31:884-96 pubmed publisher..Here, we show that a component of the siRNA loading complex, R2D2, is essential both to load endogenously encoded siRNAs (endo-siRNAs) into AGO2 and to prevent endo-siRNAs from ..
- Murchison E, Hannon G. miRNAs on the move: miRNA biogenesis and the RNAi machinery. Curr Opin Cell Biol. 2004;16:223-9 pubmed..MicroRNA functional analyses and genetic and biochemical interrogation of components of the pathway are starting to provide a glimpse at the range of biological processes and phenomena regulated by RNA interference. ..
- Kolaczkowski B, Hupalo D, Kern A. Recurrent adaptation in RNA interference genes across the Drosophila phylogeny. Mol Biol Evol. 2011;28:1033-42 pubmed publisher..Our observations suggest a predictive model of how selective pressures generated by evolutionary arms race scenarios may affect multiple genes across protein interaction networks and other biochemical pathways. ..
- Filipowicz W. RNAi: the nuts and bolts of the RISC machine. Cell. 2005;122:17-20 pubmed
- Obbard D, Gordon K, Buck A, Jiggins F. The evolution of RNAi as a defence against viruses and transposable elements. Philos Trans R Soc Lond B Biol Sci. 2009;364:99-115 pubmed publisher..Over longer time scales, key RNAi genes are repeatedly duplicated or lost across the metazoan phylogeny, with important implications for RNAi as an immune defence. ..
- Josse T, Teysset L, Todeschini A, Sidor C, Anxolabehere D, Ronsseray S. Telomeric trans-silencing: an epigenetic repression combining RNA silencing and heterochromatin formation. PLoS Genet. 2007;3:1633-43 pubmed..In contrast, TSE is not sensitive to mutations affecting r2d2, which is involved in the small interfering RNA (or siRNA) silencing pathway, nor is it sensitive to a mutation in ..
- Thomsen S, Anders S, Janga S, Huber W, Alonso C. Genome-wide analysis of mRNA decay patterns during early Drosophila development. Genome Biol. 2010;11:R93 pubmed publisher..Our data also provide a valuable resource for further experimental and computational studies investigating the process of mRNA decay. ..
- Bronkhorst A, Van Rij R. The long and short of antiviral defense: small RNA-based immunity in insects. Curr Opin Virol. 2014;7:19-28 pubmed publisher..Here, we review recent insights into the mechanism of antiviral RNAi, viral small RNA profiles, and viral counter-defense mechanisms in insects. ..
- Eleftherianos I, Won S, Chtarbanova S, Squiban B, Ocorr K, Bodmer R, et al. ATP-sensitive potassium channel (K(ATP))-dependent regulation of cardiotropic viral infections. Proc Natl Acad Sci U S A. 2011;108:12024-9 pubmed publisher..The effect of K(ATP) channels is dependent on the RNA interference genes Dcr-2, AGO2, and r2d2, indicating that an activity associated with this potassium channel participates in this antiviral pathway in ..
- Preall J, Sontheimer E. RNAi: RISC gets loaded. Cell. 2005;123:543-5 pubmed..2005) reveal the fate of the rejected passenger siRNA strand. Additionally, Gregory et al. (2005) define a heterotrimeric complex from humans that appears to execute dsRNA loading, strand selection, and target mRNA cleavage activities. ..
- Tijsterman M, Plasterk R. Dicers at RISC; the mechanism of RNAi. Cell. 2004;117:1-3 pubmed..Two papers in this issue of Cell now demonstrate that Dicer is also essential for the execution phase of RNAi and explore the distinct requirements for Dicers in the siRNA and miRNA pathways. ..
- Gerbasi V, Golden D, Hurtado S, Sontheimer E. Proteomics identification of Drosophila small interfering RNA-associated factors. Mol Cell Proteomics. 2010;9:1866-72 pubmed publisher..Dicer-2, R2D2, Loquacious, and Argonaute-2 are examples of RISC-associated factors that are involved in RNAi...
- Liu Y, Tan H, Tian H, Liang C, Chen S, Liu Q. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis. Mol Cell. 2011;44:502-8 pubmed publisher..Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. ..
- Bogerd H, Whisnant A, Kennedy E, Flores O, Cullen B. Derivation and characterization of Dicer- and microRNA-deficient human cells. RNA. 2014;20:923-37 pubmed publisher..In contrast, Drosophila Dicer 2, even in the presence of its cofactors Loqs-PD and R2D2, was unable to support human pre-miRNA processing...
- Fukunaga R, Zamore P. A universal small molecule, inorganic phosphate, restricts the substrate specificity of Dicer-2 in small RNA biogenesis. Cell Cycle. 2014;13:1671-6 pubmed publisher..Thus, a small molecule can alter the substrate specificity of a nucleic acid-processing enzyme. ..
- Mirkovic H sle M, F rstemann K. Transposon defense by endo-siRNAs, piRNAs and somatic pilRNAs in Drosophila: contributions of Loqs-PD and R2D2. PLoS ONE. 2014;9:e84994 pubmed publisher..involves the Dicer-2 co-factors Loqs-PD, which acts predominantly during processing of dsRNA by Dcr-2, and R2D2, which primarily helps to direct siRNAs into the RNA interference effector Ago2...
- Lim S, Scott A, Xiong X, Vahidpour S, Karijolich J, Guo D, et al. Requirement for CRIF1 in RNA interference and Dicer-2 stability. RNA Biol. 2014;11:1171-9 pubmed publisher..Moreover, we show that dCRIF may function by interacting with, and stabilizing, the RNase III enzyme Dicer-2. Our results suggest that dCRIF may play an important role in regulating the RNAi pathway. ..
- Preall J, He Z, Gorra J, Sontheimer E. Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila. Curr Biol. 2006;16:530-5 pubmed..In Drosophila, Dcr-2/R2D2 processes siRNAs from longer double-stranded RNAs (dsRNAs) and also nucleates RISC assembly, suggesting that ..
- Pham J, Sontheimer E. Molecular requirements for RNA-induced silencing complex assembly in the Drosophila RNA interference pathway. J Biol Chem. 2005;280:39278-83 pubmed..Here we show that R1 forms when the Dicer-2/R2D2 heterodimer binds short interfering RNA (siRNA) duplexes...
- Okamura K, Ladewig E, Zhou L, Lai E. Functional small RNAs are generated from select miRNA hairpin loops in flies and mammals. Genes Dev. 2013;27:778-92 pubmed publisher..Altogether, we reveal a conserved mechanism that yields functional RNAs from miRNA loop regions, broadening the repertoire of Argonaute-dependent regulatory RNAs and providing evidence for functionality of endogenous ssRNA species...
- Lakatos L, Csorba T, Pantaleo V, Chapman E, Carrington J, Liu Y, et al. Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors. EMBO J. 2006;25:2768-80 pubmed..None of the suppressors affected the activity of preassembled RISC complexes. In contrast, each suppressor uniformly inhibited the siRNA-initiated RISC assembly pathway by preventing RNA silencing initiator complex formation. ..
- Iwasaki S, Sasaki H, Sakaguchi Y, Suzuki T, Tadakuma H, Tomari Y. Defining fundamental steps in the assembly of the Drosophila RNAi enzyme complex. Nature. 2015;521:533-6 pubmed publisher..Although loading of siRNA duplexes into Drosophila Ago2 requires the Dicer-2-R2D2 heterodimer and the Hsc70/Hsp90 (Hsp90 also known as Hsp83) chaperone machinery, the details of RISC assembly ..
- Menon D, Meller V. A role for siRNA in X-chromosome dosage compensation in Drosophila melanogaster. Genetics. 2012;191:1023-8 pubmed publisher..Our findings are consistent with a role for siRNA in selective recognition of X chromatin. ..
- Dueck A, Meister G. Assembly and function of small RNA - argonaute protein complexes. Biol Chem. 2014;395:611-29 pubmed publisher..This review will focus on the mechanisms of Argonaute loading in different organisms. Furthermore, we highlight the versatile functions of small RNA-Argonaute protein complexes in organisms from all three kingdoms of life. ..
- Ruby J, Jan C, Bartel D. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448:83-6 pubmed..This suggests that other lineages with many similarly sized introns probably also have mirtrons, and that the mirtron pathway could have provided an early avenue for the emergence of miRNAs before the advent of Drosha. ..
- Chak L, Mohammed J, Lai E, Tucker Kellogg G, Okamura K. A deeply conserved, noncanonical miRNA hosted by ribosomal DNA. RNA. 2015;21:375-84 pubmed publisher..Our results suggest that biologically active miRNA genes may remain unidentified even in well-studied organisms. ..