Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.

By Richard I. Gregory, T. Chendrimada, Neil Cooch, R. Shiekhattar. Cell, 2005

1,630 citations recorded by the source corpus.

RNA interference is implemented through the action of the RNA-induced silencing complex (RISC). Although Argonaute2 has been identified as the catalytic center of RISC, the RISC polypeptide composition and assembly using short interfering RNA (siRNA) duplexes has remained elusive. Here we show that RISC is composed of Dicer, the double-stranded RNA binding protein TRBP, and Argonaute2. We demonstrate that this complex can cleave target RNA using precursor microRNA (pre-miRNA) hairpin as the source of siRNA. Although RISC can also utilize duplex siRNA, it displays a nearly 10-fold greater activity using the pre-miRNA Dicer substrate. RISC distinguishes the guide strand of the siRNA from the passenger strand and specifically incorporates the guide strand. Importantly, ATP is not required for miRNA processing, RISC assembly, or multiple rounds of target-RNA cleavage. These results define the composition of RISC and demonstrate that miRNA processing and target-RNA cleavage are coupled.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b4fce80f3eaee2c04cca6e4478241c6f3ad0043d

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Citations in the corpus

RNA-binding protein Dnd1 inhibits microRNA access to target mRNA. (2007, background): “Repressed mRNAs, miRNAs, and most proteins constituting the miRNA-RISC complex (miRNP) are enriched in cytoplasmic processing bodies called P bodies.”
microRNAs as oncogenes and tumor suppressors. (2007, background): “The mature miRNAs are asymmetrically incorporated into the RNA-induced silencing complex (RISC) where they regulate gene expression by mRNA degradation or translational repression while the miRNA* is quickly degraded (Gregory et al., 2005; Lin et al., 2005).”
Extensive post-transcriptional regulation of microRNAs and its implications for cancer. (2006, background): “In a concerted reaction, this siRNA-like product is loaded into the RNA induced silencing complex (RISC), where it mediates target mRNA translational suppression (Du and Zamore 2005; Gregory et al. 2005; Maniataki and Mourelatos 2005).”
A three-dimensional view of the molecular machinery of RNA interference (2009, background): “In human cells, the RISC-loading complex consists of an Argonaute protein, Dicer and the dsRBD-containing protein TRP”
MicroRNA: Biogenesis, Function and Role in Cancer (2010, background): “There is a consensus within the literature that TRBP associates with Ago2 and Dicer to play an integral role in the miRNA pathway [109, 118, 125, 126].”
MicroRNAs in cell proliferation, cell death, and tumorigenesis (2006, background): “Nevertheless, the broad significance of these findings was not fully appreciated until hundreds of similar small RNAs were identified in C. elegans, Drosophila, and mammals by molecular cloning and bioinformatics analyses in 2001 (reviewed in Bartel, 2004).”
The role of PACT in the RNA silencing pathway (2006, result): “Comparable results were reported recently by other groups (Gregory et al, 2005; Maniataki and Mourelatos, 2005; Meister et al, 2005).”
microRNA as Biomarkers and Diagnostics (2016, background): “The silencing mechanism may be determined by the extent of base pairing between themiRNAand the targetmRNAwhenmRNAbinds to the complimentary target sites located in the 3’ untranslated region of the target mRNA (Ambros, 2004; Gregory et al., 2005).”
A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses. (2006, background): “…the RNase Dicer, which processes the pre-miRNA into the mature effector z 22-nt miRNA molecule (Bernstein et al. 2001; Grishok et al. 2001; Hutvagner et al. 2001; Ketting et al. 2001; Chendrimada et al. 2005; Forstemann et al. 2005; Gregory et al. 2005; Jiang et al. 2005; Saito et al. 2005).”
Oncogenic Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms (2011, neutral): “Basepairing between themiRNA and target mRNA guides RISC to complementary transcripts, leading to gene repression through mRNA degradation and/or translational repression (Krol et al., 2010).”