Role for a bidentate ribonuclease in the initiation step of RNA interference

  title={Role for a bidentate ribonuclease in the initiation step of RNA interference},
  author={Emily Bernstein and Amy A. Caudy and Scott M. Hammond and Gregory J. Hannon},
RNA interference (RNAi) is the mechanism through which double-stranded RNAs silence cognate genes. In plants, this can occur at both the transcriptional and the post-transcriptional levels; however, in animals, only post-transcriptional RNAi has been reported to date. In both plants and animals, RNAi is characterized by the presence of RNAs of about 22 nucleotides in length that are homologous to the gene that is being suppressed. These 22-nucleotide sequences serve as guide sequences that… 

RNA silencing in Drosophila

A model in which the siRNAs interact through complementarity with the target RNA and are extended by a cellular RNA-dependent RNA polymerase (RdRP) to form a critical length of dsRNA that is subsequently degraded by RNase III-related enzymes is proposed and compared to the proposed scheme for RNA silencing in mammalian systems.

RNA Silencing Pathways in Schizosaccharomyces pombe and Drosophila melanogaster : A Dissertation

The Schizosaccharomyces pombe genome encodes only one of each of the three major classes of proteins implicated in RNA silencing: Dicer, RdRP and Argonaute, and these three proteins are required for silencing at centromeres and for the initiation of transcriptionally silent heterochromatin at the mating-type locus.

The Structure of an RNAi Polymerase Links RNA Silencing and Transcription

The 2.3-Å resolution crystal structure of QDE-1, a cRdRP from Neurospora crassa, is reported and it is found that it forms a relatively compact dimeric molecule, each subunit with a catalytic apparatus and protein fold strikingly similar to the catalytic core of the DNA-dependent RNA polymerases responsible for transcription.

Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease III ortholog involved in RNA interference

The highly conserved set of functional domains and the occurrence of a single-copy gene strongly indicate that the encoded protein is the RNase III ortholog responsible for dsRNA processing in the RNAi pathway.

RNA Interference and Its Applications

Because of its exquisite specificity and efficiency, RNAi is being considered as valuable research tool, not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes.

Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi

Biochemical purification of the RNAi effector nuclease from cultured Drosophila cells reveals that one constituent of this complex is a member of the Argonaute family of proteins, which are essential for gene silencing in Caenorhabditis elegans, Neurospora, and Arabidopsis.

Endogenous antiviral mechanisms of RNA interference: a comparative biology perspective.

The literature in this field is reviewed, which may open doors to the many uses to which this important technology is being put, including the potential of RNAi as a therapeutic strategy for gene regulation to modulate host-pathogen interactions.

Biochemical Mechanism of RNA Interference in Higher Organisms: A Dissertation

Designing siRNAs that target the single nucleotide polymorphism in superoxide dismutase that causes the familial form of amyotrophic lateral sclerosis (ALS), but leave the wild-type mRNA intact and functional is used.

An unusual Dicer-like1 protein fuels the RNA interference pathway in Trypanosoma brucei.

There is evidence that TbDcl1 is required for the generation of siRNA-size molecules and for RNAi, and the identification and functional characterization of a T. brucei Dicer-like enzyme is reported, specific to trypanosomatids.

The diverse roles of RNA helicases in RNAi

RNA interference (RNAi) is a regulatory gene silencing system found in nearly all eukaryotic organisms that employs small RNAs, typically 20-25 nucleotides long, to target complementary sequences



An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells

It is shown that ‘loss-of-function’ phenotypes can be created in cultured Drosophila cells by transfection with specific double-stranded RNAs, which coincides with a marked reduction in the level of cognate cellular messenger RNAs.

Function, mechanism and regulation of bacterial ribonucleases.

RNase III provides an important model with which to understand mechanisms of RNA maturation, RNA decay, and gene regulation, and is regulated by phosphorylation in the T7 phage- infected cell.

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

Targeted mRNA degradation by double-stranded RNA in vitro.

The development of a cell-free system from syncytial blastoderm Drosophila embryos that recapitulates many of the features of RNAi is reported, demonstrating that RNAi can be mediated by sequence-specific processes in soluble reactions.

RNAi and double-strand RNA.

dsRNA mediated suppression of specific gene expression has also been observed in plants and one demonstration of the phenomenon follows expression in plant cells of a recombinant RNA virus containing exonic sequences of an endogenous cellular gene.

Post‐transcriptional gene‐silencing: RNAs on the attack or on the defense?

  • T. SijenJ. Kooter
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2000
The natural role of Post‐transcriptional gene‐silencing seems to be as a defence against plant viruses, so what first appeared to be RNAs on the attack may now be considered RN as on the defense.

AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals.

The isolation of Arabidopsis mutants impaired in PTGS and Sequencing of ago1 mutants revealed one amino acid essential for PTGS that is also present in QDE-2 and RDE-1 in a highly conserved motif confirm the hypothesis that these processes derive from a common ancestral mechanism that controls expression of invading nucleic acid molecules at the post-transcriptional level.