ERIK SONTHEIMER

..Fang et al. now reveal a set of Piwi-interacting RNAs (piRNAs) in Oxytricha trifallax that likewise enable genomic self versus nonself discrimination, this time by specifying self sequences for genome retention...

..Bioinformatic analyses indicate that target genes in vertebrate species may number in the thousands...

..These advances have taken our mechanistic understanding of RNA interference to a new level and promise to improve our ability to exploit this biological process for use in experimental biology and medicine...

..Combined dsRNA-processing/mRNA-cleavage assays indicate that siRNA strand selection is independent of dsRNA processing polarity during Drosophila RISC assembly in vitro...

..A recent report in Cell reveals how Dicer's two RNase III domains collaborate during dsRNA processing and sets the stage for a deeper understanding of Dicer's roles in later phases of silencing complex assembly...

..Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment...

..Differential complementarity outside of the spacer sequence is a built-in feature of all CRISPR systems, indicating that this mechanism is a broadly applicable solution to the self/non-self dilemma that confronts all immune pathways...

..However, Dicer-1 but not Dicer-2 is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila...

..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...

..We suggest that the recycling of RISCs is promoted by MVBs, resulting in RISCs more effectively engaging with small RNA effectors and possibly target RNAs. It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm...

..We conclude that CRISPR loci counteract multiple routes of HGT and can limit the spread of antibiotic resistance in pathogenic bacteria...

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..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...

..Now, Liu et al. identify R2D2, a Dicer-associated protein that is important for siRNA incorporation into RISC, thus linking the initiation and execution phases of RNAi...

..Complex D could impinge upon the RISC assembly pathway in humans, similar to an analogous complex in Drosophila...

..Our results define a new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing machinery...

..Recent work in flies and mice reveals several classes of endogenous siRNAs (endo-siRNAs) that contribute to functions previously reserved for miRNAs and piRNAs, including gene regulation and transposon suppression...

..describe the structure and activity of Cas1, the only protein associated with all CRISPR loci. Cas1 is a metal-dependent deoxyribonuclease, consistent with a role in the adaptation phase of CRISPR immunity against invading nucleic acids...

..These results indicate that 2'-ureido modifications are superior to analogous 2'-amido ones for applications that require stable base pairing...

..The proposed studies will clarify the molecular basis for CRISPR function and will therefore contribute to our ability to exploit this natural pathway to prevent or treat infectious disease. ..

..Accordingly, a deeper understanding of RNA silencing pathways will accelerate many aspects of biomedical research and disease treatment. ..

..Development of compounds that boost RNAi performance in general will have significant impact on public health. ..