Mechanistic insights into RNA cleavage by human Argonaute2–siRNA complex

Meister, G. Argonaute proteins: Functional insights and emerging roles. Nat. Rev. Genet. 14, 447–459 (2013).

Article  CAS  PubMed  Google Scholar 

Wang, X., Ramat, A., Simonelig, M. & Liu, M. F. Emerging roles and functional mechanisms of PIWI-interacting RNAs. Nat. Rev. Mol. Cell Biol. 24, 123–141 (2023).

Article  CAS  PubMed  Google Scholar 

Bartel, D. P. Metazoan microRNAs. Cell 173, 20–51 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tang, G. siRNA and miRNA: An insight into RISCs. Trends Biochem. Sci. 30, 106–114 (2005).

Article  CAS  PubMed  Google Scholar 

Ghildiyal, M., Xu, J., Seitz, H., Weng, Z. & Zamore, P. D. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA 16, 43–56 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ozata, D. M., Gainetdinov, I., Zoch, A., O’Carroll, D. & Zamore, P. D. PIWI-interacting RNAs: small RNAs with big functions. Nat. Rev. Genet. 20, 89–108 (2019).

Article  CAS  PubMed  Google Scholar 

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 

Carthew, R. W. & Sontheimer, E. J. Origins and mechanisms of miRNAs and siRNAs. Cell 136, 642–655 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eichhorn, S. W. et al. MRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol. Cell 56, 104–115 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bazzini, A. A., Lee, M. T. & Giraldez, A. J. Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. Science 336, 233–237 (2012).

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  CAS  PubMed  Google Scholar 

Djuranovic, S., Nahvi, A. & Green, R. miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336, 237–240 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Haley, B. & Zamore, P. D. Kinetic analysis of the RNAi enzyme complex. Nat. Struct. Mol. Biol. 11, 599–606 (2004).

Article  CAS  PubMed  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 

Chiu, Y. L. & Rana, T. M. siRNA function in RNAi: A chemical modification analysis. RNA 9, 1034–1048 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zamore, P. D., Tuschl, T., Sharp, P. A. & Bartel, D. P. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25–33 (2000).

Article  CAS  PubMed  Google Scholar 

Jadhav, V., Vaishnaw, A., Fitzgerald, K. & Maier, M. A. RNA interference in the era of nucleic acid therapeutics. Nat. Biotechnol. 42, 394–405 (2024).

Article  CAS  PubMed  Google Scholar 

Wilkins, C. et al. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436, 1044–1047 (2005).

Article  CAS  PubMed  Google Scholar 

Wang, X. H. et al. RNA interference directs innate immunity against viruses in adult Drosophila. Science 312, 452–454 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cheloufi, S., Dos Santos, C. O., Chong, M. M. W. & Hannon, G. J. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 465, 584–589 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cifuentes, D. et al. A novel miRNA processing pathway independent of dicer requires argonaute2 catalytic activity. Science 328, 1694–1698 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yang, S. et al. Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis. Proc. Natl. Acad. Sci. USA 107, 15163–15168 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jee, D. et al. Dual strategies for argonaute2-mediated biogenesis of erythroid miRNAs underlie conserved requirements for slicing in mammals. Mol. Cell 69, 265–278.e6 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Elkayam, E. et al. The structure of human argonaute-2 in complex with miR-20a. Cell 150, 100–110 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schirle, N. T. & MacRae, I. J. The crystal structure of human argonaute2. Science 336, 1037–1040 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schirle, N. T., Sheu-Gruttadauria, J. & MacRae, I. J. Structural basis for microRNA targeting. Science 346, 608–613 (2014).

Article  CAS  PubMed  PubMed Central  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 

Wee, L. M., Flores-Jasso, C. F., Salomon, W. E. & Zamore, P. D. Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties. Cell 151, 1055–1067 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Becker, W. R. et al. High-throughput analysis reveals rules for target RNA binding and cleavage by AGO2. Mol. Cell 75, 741–755.e11 (2019).

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 

Comments (0)

No login
gif