A three-dimensional view of the molecular machinery of RNA interference (original) (raw)

• Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20 (2005).
  Article CAS PubMed Google Scholar
• Stefani, G. & Slack, F. J. Small non-coding RNAs in animal development. Nature Rev. Mol. Cell Biol. 9, 219–230 (2008).
  Article CAS Google Scholar
• Bernstein, E., Caudy, A. A., Hammond, S. M. & Hannon, G. J. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363–366 (2001).
  Article ADS CAS PubMed Google Scholar
• Hutvagner, G. & Simard, M. J. Argonaute proteins: key players in RNA silencing. Nature Rev. Mol. Cell Biol. 9, 22–32 (2008).
  Article CAS Google Scholar
• Grewal, S. I. & Elgin, S. C. Transcription and RNA interference in the formation of heterochromatin. Nature 447, 399–406 (2007).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Klattenhoff, C. & Theurkauf, W. Biogenesis and germline functions of piRNAs. Development 135, 3–9 (2008).
  Article CAS PubMed Google Scholar
• Haasnoot, J., Westerhout, E. M. & Berkhout, B. RNA interference against viruses: strike and counterstrike. Nature Biotechnol. 25, 1435–1443 (2007).
  Article CAS Google Scholar
• Li, F. & Ding, S. W. Virus counterdefense: diverse strategies for evading the RNA-silencing immunity. Annu. Rev. Microbiol. 60, 503–531 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, Y. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 425, 415–419 (2003).
  Article ADS CAS PubMed Google Scholar
• Nykänen, A., Haley, B. & Zamore, P. D. ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell 107, 309–321 (2001).
  Article PubMed Google Scholar
• Elbashir, S. M., Lendeckel, W. & Tuschl, T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 15, 188–200 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W. & Tuschl, T. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 20, 6877–6888 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Macrae, I. J. & Doudna, J. A. Ribonuclease revisited: structural insights into ribonuclease III family enzymes. Curr. Opin. Struct. Biol. 17, 138–145 (2007).
  Article CAS PubMed Google Scholar
• Blaszczyk, J. et al. Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage. Structure 9, 1225–1236 (2001).
  Article CAS PubMed Google Scholar
• Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E. & Filipowicz, W. Single processing center models for human Dicer and bacterial RNase III. Cell 118, 57–68 (2004). This paper elegantly showed that Dicer contains a single processing centre and proposed that the two RNaseIII domains of Dicer function as an intramolecular dimer.
  Article CAS PubMed Google Scholar
• Gan, J. et al. Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III. Cell 124, 355–366 (2006).
  Article CAS PubMed Google Scholar
• Lingel, A., Simon, B., Izaurralde, E. & Sattler, M. Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature 426, 465–469 (2003).
  Article ADS CAS PubMed Google Scholar
• Yan, K. S. et al. Structure and conserved RNA binding of the PAZ domain. Nature 426, 468–474 (2003).
  Article ADS PubMed CAS Google Scholar
• Song, J. J. et al. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nature Struct. Biol. 10, 1026–1032 (2003).
  Article CAS PubMed Google Scholar
• Macrae, I. J. et al. Structural basis for double-stranded RNA processing by Dicer. Science 311, 195–198 (2006). This paper described the three-dimensional architecture of Dicer, revealing how Dicer functions as a molecular ruler to determine the length of its dsRNA products.
  Article ADS CAS PubMed Google Scholar
• Macrae, I. J., Zhou, K. & Doudna, J. A. Structural determinants of RNA recognition and cleavage by Dicer. Nature Struct. Mol. Biol. 14, 934–940 (2007).
  Article CAS Google Scholar
• Ma, J. B., Ye, K. & Patel, D. J. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 429, 318–322 (2004). This paper revealed the mode of recognition of the 3′ end of siRNAs by the PAZ domain, identifying conserved residues that bind the 3′ nucleotide.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Lingel, A., Simon, B., Izaurralde, E. & Sattler, M. Nucleic acid 3′-end recognition by the Argonaute2 PAZ domain. Nature Struct. Mol. Biol. 11, 576–577 (2004). This paper showed that the PAZ domain provides a conserved hydrophobic binding pocket for the 3′ nucleotide of ssRNA.
  Article CAS Google Scholar
• Du, Z., Lee, J. K., Tjhen, R., Stroud, R. M. & James, T. L. Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage. Proc. Natl Acad. Sci. USA 105, 2391–2396 (2008).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Ma, E., Macrae, I. J., Kirsch, J. F. & Doudna, J. A. Autoinhibition of human Dicer by its internal helicase domain. J. Mol. Biol. 380, 237–243 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Jankowsky, E. & Fairman, M. E. RNA helicases — one fold for many functions. Curr. Opin. Struct. Biol. 17, 316–324 (2007).
  Article CAS PubMed Google Scholar
• Provost, P. et al. Ribonuclease activity and RNA binding of recombinant human Dicer. EMBO J. 21, 5864–5874 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, H., Kolb, F. A., Brondani, V., Billy, E. & Filipowicz, W. Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. EMBO J. 21, 5875–5885 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Han, J. et al. The Drosha–DGCR8 complex in primary microRNA processing. Genes Dev. 18, 3016–3027 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Gregory, R. I. et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 432, 235–240 (2004).
  Article ADS CAS PubMed Google Scholar
• Han, J. et al. Molecular basis for the recognition of primary microRNAs by the Drosha–DGCR8 complex. Cell 125, 887–901 (2006).
  Article CAS PubMed Google Scholar
• Sohn, S. Y. et al. Crystal structure of human DGCR8 core. Nature Struct. Mol. Biol. 14, 847–853 (2007).
  Article CAS Google Scholar
• Farazi, T. A., Juranek, S. A. & Tuschl, T. The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 135, 1201–1214 (2008).
  Article CAS PubMed Google Scholar
• Brennecke, J. et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila . Cell 128, 1089–1103 (2007).
  Article CAS PubMed Google Scholar
• Gunawardane, L. S. et al. A slicer-mediated mechanism for repeat-associated siRNA 5′ end formation in Drosophila . Science 315, 1587–1590 (2007).
  Article ADS CAS PubMed Google Scholar
• Hutvágner, G. & Zamore, P. D. A microRNA in a multiple-turnover RNAi enzyme complex. Science 297, 2056–2060 (2002).
  Article ADS PubMed CAS Google Scholar
• Doench, J. G., Petersen, C. P. & Sharp, P. A. siRNAs can function as miRNAs. Genes Dev. 17, 438–442 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Chiu, Y. L. & Rana, T. M. RNAi in human cells: basic structural and functional features of small interfering RNA. Mol. Cell 10, 549–561 (2002).
  Article CAS PubMed Google Scholar
• Jackson, R. J. & Standart, N. How do microRNAs regulate gene expression? Sci. STKE 2007, re1 (2007).
  Article PubMed Google Scholar
• Cerutti, L., Mian, N. & Bateman, A. Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. Trends Biochem. Sci. 25, 481–482 (2000).
  Article CAS PubMed Google Scholar
• Song, J. J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434–1437 (2004). This paper revealed the molecular architecture of Argonaute proteins and showed that the PIWI domain resembles RNaseH, suggesting that Argonaute is the 'slicer'.
  Article ADS CAS PubMed Google Scholar
• Nowotny, M., Gaidamakov, S. A., Crouch, R. J. & Yang, W. Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121, 1005–1016 (2005).
  Article CAS PubMed Google Scholar
• Parker, J. S., Roe, S. M. & Barford, D. Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. EMBO J. 23, 4727–4237 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Yuan, Y. R. et al. Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol. Cell 19, 405–419 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Ma, J. B. et al. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434, 666–670 (2005). This paper revealed that the 5′ phosphate group of the guide RNA strand binds to a pocket at the interface of the MID and PIWI domains in the A. fulgidus Piwi protein and that the first nucleotide of the guide strand does not base-pair with the target RNA.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004). This paper showed that human AGO2 has slicer activity and that mutations in its PIWI domain, based on the structure of archaeal Argonaute, abolish RISC activity in vivo.
  Article ADS CAS PubMed Google Scholar
• Martinez, J. & Tuschl, T. RISC is a 5′ phosphomonoester-producing RNA endonuclease. Genes Dev. 18, 975–980 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Schwarz, D. S., Tomari, Y. & Zamore, P. D. The RNA-induced silencing complex is a Mg2+-dependent endonuclease. Curr. Biol. 14, 787–791 (2004).
  Article CAS PubMed Google Scholar
• Rivas, F. V. et al. Purified Argonaute2 and an siRNA form recombinant human RISC. Nature Struct. Mol. Biol. 12, 340–349 (2005).
  Article CAS Google Scholar
• Irvine, D. V. et al. Argonaute slicing is required for heterochromatic silencing and spreading. Science 313, 1134–1137 (2006).
  Article ADS CAS PubMed Google Scholar
• Meister, G. et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15, 185–197 (2004).
  Article CAS PubMed Google Scholar
• Saito, K. et al. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev. 20, 2214–2222 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Förstemann, K., Horwich, M. D., Wee, L., Tomari, Y. & Zamore, P. D. Drosophila microRNAs are sorted into functionally distinct Argonaute complexes after production by Dicer-1. Cell 130, 287–297 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001).
  Article ADS CAS PubMed Google Scholar
• Parker, J. S., Roe, S. M. & Barford, D. Structural insights into mRNA recognition from a PIWI domain–siRNA guide complex. Nature 434, 663–666 (2005). The paper revealed how the 5′ phosphate group of the guide RNA strand is recognized by Argonaute, and it highlights the importance of the seed region in mediating guide-target recognition.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Haley, B. & Zamore, P. D. Kinetic analysis of the RNAi enzyme complex. Nature Struct. Mol. Biol. 11, 599–606 (2004).
  Article CAS Google Scholar
• Mi, S. et al. Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell 133, 116–127 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Montgomery, T. A. et al. Specificity of ARGONAUTE7–miR390 interaction and dual functionality in _TAS3 trans_-acting siRNA formation. Cell 133, 128–141 (2008).
  Article CAS PubMed Google Scholar
• Ohara, T. et al. The 3′ termini of mouse Piwi-interacting RNAs are 2′-O-methylated. Nature Struct. Mol. Biol. 14, 349–350 (2007).
  Article CAS Google Scholar
• Kirino, Y. & Mourelatos, Z. Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′ termini. Nature Struct. Mol. Biol. 14, 347–348 (2007).
  Article CAS Google Scholar
• Schwarz, D. S. et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115, 199–208 (2003).
  Article CAS PubMed Google Scholar
• Miyoshi, K., Tsukumo, H., Nagami, T., Siomi, H. & Siomi, M. C. Slicer function of Drosophila Argonautes and its involvement in RISC formation. Genes Dev. 19, 2837–2848 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Matranga, C., Tomari, Y., Shin, C., Bartel, D. P. & Zamore, P. D. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123, 607–620 (2005).
  Article CAS PubMed Google Scholar
• Rand, T. A., Petersen, S., Du, F. & Wang, X. Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123, 621–629 (2005).
  Article CAS PubMed Google Scholar
• Leuschner, P. J., Ameres, S. L., Kueng, S. & Martinez, J. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep. 7, 314–320 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Gregory, R. I., Chendrimada, T. P., Cooch, N. & Shiekhattar, R. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123, 631–640 (2005).
  Article CAS PubMed Google Scholar
• Macrae, I. J., Ma, E., Zhou, M., Robinson, C. V. & Doudna, J. A. In vitro reconstitution of the human RISC-loading complex. Proc. Natl Acad. Sci. USA 105, 512–517 (2008).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Maniataki, E. & Mourelatos, Z. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes Dev. 19, 2979–2990 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Förstemann, K. et al. Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol. 3, e236 (2005).
  Article PubMed PubMed Central CAS Google Scholar
• Saito, K., Ishizuka, A., Siomi, H. & Siomi, M. C. Processing of pre-microRNAs by the Dicer-1–Loquacious complex in Drosophila cells. PLoS Biol. 3, e235 (2005).
  Article PubMed PubMed Central CAS Google Scholar
• Jiang, F. et al. Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila . Genes Dev. 19, 1674–1679 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Tomari, Y. et al. RISC assembly defects in the Drosophila RNAi mutant armitage . Cell 116, 831–841 (2004).
  Article CAS PubMed Google Scholar
• Liu, X., Jiang, F., Kalidas, S., Smith, D. & Liu, Q. Dicer-2 and R2D2 coordinately bind siRNA to promote assembly of the siRISC complexes. RNA 12, 1514–1520 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, Q. et al. R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301, 1921–1925 (2003).
  Article ADS CAS PubMed Google Scholar
• Tomari, Y., Du, T. & Zamore, P. D. Sorting of Drosophila small silencing RNAs. Cell 130, 299–308 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Stark, A., Brennecke, J., Russell, R. B. & Cohen, S. M. Identification of Drosophila microRNA targets. PLoS Biol. 1, e60 (2003).
  Article PubMed PubMed Central Google Scholar
• Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P. & Burge, C. B. Prediction of mammalian microRNA targets. Cell 115, 787–798 (2003).
  Article CAS PubMed Google Scholar
• Doench, J. G. & Sharp, P. A. Specificity of microRNA target selection in translational repression. Genes Dev. 18, 504–511 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, Y., Sheng, G., Juranek, S. A., Tuschl, T. & Patel, D.J. Structure of the guide-strand-containing argonaute silencing complex. Nature 456, 209–213 (2008). This paper revealed that binding of the guide strand to Argonaute orders the seed region in a helical conformation, poised to initiate base-pairing with the target strand.
  Article ADS CAS PubMed PubMed Central Google Scholar
• Wang, Y. et al. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456, 921–926 (2008).
  Article ADS CAS PubMed PubMed Central Google Scholar
• Filipowicz, W. RNAi: the nuts and bolts of the RISC machine. Cell 122, 17–20 (2005).
  Article CAS PubMed Google Scholar
• Tomari, Y. & Zamore, P. D. Machines for RNAi. Genes Dev. 19, 517–529 (2005).
  Article CAS PubMed Google Scholar
• Pillai, R. S., Artus, C. G. & Filipowicz, W. Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis. RNA 10, 1518–1525 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Mathonnet, G. et al. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317, 1764–1767 (2007).
  Article ADS CAS PubMed Google Scholar
• Kiriakidou, M. et al. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129, 1141–1151 (2007).
  Article CAS PubMed Google Scholar
• Jakymiw, A. et al. Disruption of GW bodies impairs mammalian RNA interference. Nature Cell Biol. 7, 1267–1274 (2005).
  Article PubMed CAS Google Scholar
• Behm-Ansmant, I. et al. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev. 20, 1885–1898 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Liu, J. et al. A role for the P-body component GW182 in microRNA function. Nature Cell Biol. 7, 1261–1266 (2005).
  Article PubMed CAS Google Scholar
• Eulalio, A., Huntzinger, E. & Izaurralde, E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nature Struct. Mol. Biol. 15, 346–353 (2008).
  Article CAS Google Scholar
• Till, S. et al. A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain. Nature Struct. Mol. Biol. 14, 897–903 (2007).
  Article CAS Google Scholar
• Meister, G. et al. Identification of novel argonaute-associated proteins. Curr. Biol. 15, 2149–2155 (2005).
  Article CAS PubMed Google Scholar
• Höck, J. et al. Proteomic and functional analysis of Argonaute-containing mRNA–protein complexes in human cells. EMBO Rep. 8, 1052–1060 (2007).
  Article PubMed PubMed Central CAS Google Scholar