Biophysics of RNA-Protein Interactions pp 167-188 | Cite as
Biophysical and Biochemical Approaches in the Analysis of Argonaute–MicroRNA Complexes
- 460 Downloads
Abstract
MicroRNAs (miRNAs) are a class of small, noncoding, and single-stranded RNAs that play a key role in regulating gene expressions in most eukaryotes. Human genome encodes over 1,600 different miRNA loci, and miRNAs directly regulate expression of over 60% of protein-coding genes. The canonical miRNA biogenesis pathway has been well documented with key players identified by the efforts of many biochemical research groups. However, we still lack a mechanistic understanding of the target recognition and gene silencing processes. Over the recent years, structural, biochemical, and single-molecule biophysical studies have revealed the complexity in the interactions between miRNA and the effector protein Argonaute (Ago) as well as between Ago and the target mRNA. In this chapter, we present these findings that significantly enhanced our knowledge of the assembly and regulation by Ago–miRNA complexes.
Keywords
MicroRNA Argonaute RISC Protein structure Single-molecule experiment Speed–stability paradoxNotes
Acknowledgements
This work was supported by Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-MA1702-08.
References
- 1.Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.CrossRefGoogle Scholar
- 2.Ha, M., & Kim, V. N. (2014). Regulation of microRNA biogenesis. Nature Reviews Molecular Cell Biology, 15, 509–524.CrossRefGoogle Scholar
- 3.Cai, X., Hagedorn, C. H., & Cullen, B. R. (2004). Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA, 10, 1957–1966.CrossRefGoogle Scholar
- 4.Lee, Y., Jeon, K., Lee, J. T., Kim, S., & Kim, V. N. (2002). MicroRNA maturation: Stepwise processing and subcellular localization. The EMBO Journal, 21, 4663–4670.CrossRefGoogle Scholar
- 5.Lee, Y., et al. (2004). MicroRNA genes are transcribed by RNA polymerase II. The EMBO Journal, 23, 4051–4060.CrossRefGoogle Scholar
- 6.Ozsolak, F., et al. (2008). Chromatin structure analyses identify miRNA promoters. Genes & Development, 22, 3172–3183.CrossRefGoogle Scholar
- 7.Denli, A. M., Tops, B. B., Plasterk, R. H., Ketting, R. F., & Hannon, G. J. (2004). Processing of primary microRNAs by the microprocessor complex. Nature, 432, 231–235.ADSCrossRefGoogle Scholar
- 8.Gregory, R. I., et al. (2004). The Microprocessor complex mediates the genesis of microRNAs. Nature, 432, 235–240.ADSCrossRefGoogle Scholar
- 9.Han, J., et al. (2004). The Drosha-DGCR9 complex in primary microRNA processing. Genes & Development, 18, 3016–3027.CrossRefGoogle Scholar
- 10.Landthaler, M., Yalcin, A., & Tuschl, T. (2004). The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Current Biology, 14, 2162–2167.CrossRefGoogle Scholar
- 11.Lee, Y., et al. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425, 415–419.ADSCrossRefGoogle Scholar
- 12.Kim, B., Jeong, K., & Kim, V. N. (2017). Genome-wide mapping of DROSHA cleavage sites on primary microRNAs and noncanonical substrates. Molecular Cell, 66, 258–269. e255.CrossRefGoogle Scholar
- 13.Nguyen, T. A., et al. (2015). Functional anatomy of the human microprocessor. Cell, 161, 1374–1387.CrossRefGoogle Scholar
- 14.Kwon, S. C., et al. (2016). Structure of human DROSHA. Cell, 164, 81–90.CrossRefGoogle Scholar
- 15.Auyeung, V. C., Ulitsky, I., McGeary, S. E., & Bartel, D. P. (2013). Beyond secondary structure: Primary-sequence determinants license pri-miRNA hairpins for processing. Cell, 152, 844–858.CrossRefGoogle Scholar
- 16.Yi, R., Qin, Y., Macara, I. G., & Cullen, B. R. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development, 17, 3011–3016.CrossRefGoogle Scholar
- 17.MacRae, I. J., Zhou, K., & Doudna, J. A. (2007). Structural determinants of RNA recognition and cleavage by Dicer. Nature Structural & Molecular Biology, 14, 934–940.CrossRefGoogle Scholar
- 18.Park, J. E., et al. (2011). Dicer recognizes the 5′ end of RNA for efficient and accurate processing. Nature, 475, 201–205.CrossRefGoogle Scholar
- 19.Macrae, I. J., et al. (2006). Structural basis for double-stranded RNA processing by Dicer. Science, 311, 195–198.ADSCrossRefGoogle Scholar
- 20.Hutvagner, G., & Simard, M. J. (2008). Argonaute proteins: Key players in RNA silencing. Nature Reviews Molecular Cell Biology, 9, 22–32.CrossRefGoogle Scholar
- 21.Liu, J., et al. (2004). Arogonaute2 Is the catalytic engine of mammalian RNAi. Science, 305, 1437–1441.ADSCrossRefGoogle Scholar
- 22.Schirle, N. T., & MacRae, I. J. (2012). The crystal structure of human Argonaute2. Science, 336, 1037–1040.ADSCrossRefGoogle Scholar
- 23.Song, J. J., Smith, S. K., Hannon, G. J., & Joshua-Tor, L. (2004). Crystal structure of Argonaute and its implications for RISC slicer activity. Science, 305, 1434–1437.ADSCrossRefGoogle Scholar
- 24.Gan, H. H., & Gunsalus, K. C. (2015). Assembly and analysis of eukaryotic Argonaute-RNA complexes in microRNA-target recognition. Nucleic Acids Research, 43, 9613–9625.Google Scholar
- 25.Lingel, A., Simon, B., Izaurralde, E., & Sattler, M. (2003). Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature, 426, 465–469.ADSCrossRefGoogle Scholar
- 26.Lingel, A., Simon, B., Izaurralde, E., & Sattler, M. (2004). Nucleic acid 3′-end recognition by the Argonaute2 PAZ domain. Nature Structural & Molecular Biology, 11, 576–577.CrossRefGoogle Scholar
- 27.Ma, J. B., Ye, K., & Patel, D. J. (2004). Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature, 429, 318–322.ADSCrossRefGoogle Scholar
- 28.Ma, J. B., et al. (2005). Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature, 434, 666–670.ADSCrossRefGoogle Scholar
- 29.Parker, J. S., Roe, S. M., & Barford, D. (2004). Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. The EMBO Journal, 23, 4727–4737.CrossRefGoogle Scholar
- 30.Yuan, Y. R., et al. (2005). Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Molecular Cell, 19, 405–419.CrossRefGoogle Scholar
- 31.Jung, S. R., et al. (2013). Dynamic anchoring of the 3′-end of the guide strand controls the target dissociation of Argonaute-guide complex. The Journal of the American Chemical Society, 135, 16865–16871.CrossRefGoogle Scholar
- 32.Haley, B., & Zamore, P. D. (2004). Kinetic analysis of the RNAi enzyme complex. Nature Structural & Molecular Biology, 11, 599–606.CrossRefGoogle Scholar
- 33.Zamore, P. D. (2001). Thirty-three years later, a glimpse at the ribonuclease III active site. Molecular Cell, 8, 1158–1160.CrossRefGoogle Scholar
- 34.Elbashir, S. M. (2001). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200.CrossRefGoogle Scholar
- 35.Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W., & Tuschl, T. (2001). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. The EMBO Journal, 20, 6877–6888.CrossRefGoogle Scholar
- 36.Nykanen, A., Haley, B., & Zamore, P. D. (2001). ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell, 107, 309–321.CrossRefGoogle Scholar
- 37.Meister, G., et al. (2004). Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Molecular Cell, 15, 185–197.CrossRefGoogle Scholar
- 38.Nowotny, M., Gaidamakov, S. A., Crouch, R. J., & Yang, W. (2005). Crystal structures of RNase H bound to an RNA/DNA hybrid: Substrate specificity and metal-dependent catalysis. Cell, 121, 1005–1016.CrossRefGoogle Scholar
- 39.Rivas, F. V., et al. (2005). Purified Argonaute2 and an siRNA form recombinant human RISC. Nature Structural & Molecular Biology, 12, 340–349.CrossRefGoogle Scholar
- 40.Schwarz, D. S., Tomari, Y., & Zamore, P. D. (2004). The RNA-induced silencing complex is a Mg2+ -dependent endonuclease. Current Biology, 14, 787–791.CrossRefGoogle Scholar
- 41.Martinez, J., & Tuschl, T. (2004). RISC is a 5′ phosphomonoester-producing RNA endonuclease. Genes & Development, 18, 975–980.CrossRefGoogle Scholar
- 42.Jinek, M., & Doudna, J. A. (2009). A three-dimensional view of the molecular machinery of RNA interference. Nature, 457, 405–412.ADSCrossRefGoogle Scholar
- 43.Forstemann, K., Horwich, M. D., Wee, L., Tomari, Y., & Zamore, P. D. (2007). Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by dicer-1. Cell, 130, 287–297.CrossRefGoogle Scholar
- 44.Park, M. S., et al. (2017). Human Argonaute3 has slicer activity. Nucleic Acids Research, 45, 11867–11877.CrossRefGoogle Scholar
- 45.Wang, Y., Sheng, G., Juranek, S., Tuschl, T., & Patel, D. J. (2008). Structure of the guide-strand-containing argonaute silencing complex. Nature, 456, 209–213.ADSCrossRefGoogle Scholar
- 46.Kim, V. N. (2008). Sorting out small RNAs. Cell, 133, 25–26.CrossRefGoogle Scholar
- 47.Kiriakidou, M., et al. (2007). An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell, 129, 1141–1151.CrossRefGoogle Scholar
- 48.Frank, F., et al. (2011). Structural analysis of 5′-mRNA-cap interactions with the human AGO2 MID domain. EMBO Reports, 12, 415–420.CrossRefGoogle Scholar
- 49.Behm-Ansmant, I., et al. (2006). mRNA degradation by miRNAs and GW182 requires both CCR49:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes & Development, 20, 1885–1898.CrossRefGoogle Scholar
- 50.Braun, J. E., Huntzinger, E., Fauser, M., & Izaurralde, E. (2011). GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Molecular Cell, 44, 120–133.CrossRefGoogle Scholar
- 51.Fabian, M. R., et al. (2011). miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR51-NOT. Nature Structural & Molecular Biology, 18, 1211–1217.CrossRefGoogle Scholar
- 52.Lim, J., et al. (2014). Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell, 159, 1365–1376.CrossRefGoogle Scholar
- 53.Doench, J. G., & Sharp, P. A. (2004). Specificity of microRNA target selection in translational repression. Genes & Development, 18, 504–511.CrossRefGoogle Scholar
- 54.Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P., & Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115, 787–798.CrossRefGoogle Scholar
- 55.Stark, A., Brennecke, J., Russell, R. B., & Cohen, S. M. (2003). Identification of Drosophila microRNA targets. PLOS Biology, 1, E60.CrossRefGoogle Scholar
- 56.Gregory, R. I., Chendrimada, T. P., Cooch, N., & Shiekhattar, R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell, 123, 631–640.CrossRefGoogle Scholar
- 57.MacRae, I. J., Ma, E., Zhou, M., Robinson, C. V., & Doudna, J. A. (2008). In vitro reconstitution of the human RISC-loading complex. Proceedings of the National Academy of Sciences of the United States of America, 105, 512–517.ADSCrossRefGoogle Scholar
- 58.Maniataki, E., & Mourelatos, Z. (2005). A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes & Development, 19, 2979–2990.CrossRefGoogle Scholar
- 59.Wang, H. W., et al. (2009). Structural insights into RNA processing by the human RISC-loading complex. Nature Structural & Molecular Biology, 16, 1148–1153.CrossRefGoogle Scholar
- 60.Kanellopoulou, C., et al. (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes & Development, 19, 489–501.CrossRefGoogle Scholar
- 61.Martinez, J., Patkaniowska, A., Urlaub, H., Luhrmann, R., & Tuschl, T. (2002). Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell, 110, 563–574.CrossRefGoogle Scholar
- 62.Murchison, E. P., Partridge, J. F., Tam, O. H., Cheloufi, S., & Hannon, G. J. (2005). Characterization of Dicer-deficient murine embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 102, 12135–12140.ADSCrossRefGoogle Scholar
- 63.Ye, X., et al. (2011). Structure of C3PO and mechanism of human RISC activation. Nature Structural & Molecular Biology, 18, 650–657.CrossRefGoogle Scholar
- 64.Betancur, J. G., & Tomari, Y. (2012). Dicer is dispensable for asymmetric RISC loading in mammals. RNA, 18, 24–30.CrossRefGoogle Scholar
- 65.Cheloufi, S., Dos Santos, C. O., Chong, M. M., & Hannon, G. J. (2010). A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature, 465, 584–589.ADSCrossRefGoogle Scholar
- 66.Kim, Y., & Kim, V. N. (2012). MicroRNA factory: RISC assembly from precursor microRNAs. Molecular Cell, 46, 384–386.ADSCrossRefGoogle Scholar
- 67.Kawamata, T., & Tomari, Y. (2010). Making RISC. Trends in Biochemical Sciences, 35, 368–376.CrossRefGoogle Scholar
- 68.Tomari, Y., Matranga, C., Haley, B., Martinez, N., & Zamore, P. D. (2004). A protein sensor for siRNA asymmetry. Science, 306, 1377–1380.ADSCrossRefGoogle Scholar
- 69.Eulalio, A., Huntzinger, E., & Izaurralde, E. (2008). Getting to the root of miRNA-mediated gene silencing. Cell, 132, 9–14.CrossRefGoogle Scholar
- 70.Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nature Reviews Genetics, 9, 102–114.CrossRefGoogle Scholar
- 71.Baek, D., et al. (2008). The impact of microRNAs on protein output. Nature, 455, 64–71.ADSCrossRefGoogle Scholar
- 72.Brennecke, J., Stark, A., Russell, R. B., & Cohen, S. M. (2005). Principles of microRNA-target recognition. PLOS Biology, 3, e85.CrossRefGoogle Scholar
- 73.Selbach, M., et al. (2008). Widespread changes in protein synthesis induced by microRNAs. Nature, 455, 58–63.ADSCrossRefGoogle Scholar
- 74.Kim, D., et al. (2016). General rules for functional microRNA targeting. Nature Genetics, 48, 1517–1526.CrossRefGoogle Scholar
- 75.Schirle, N. T., Sheu-Gruttadauria, J., & MacRae, I. J. (2014). Structural basis for microRNA targeting. Science, 346, 608–613.ADSCrossRefGoogle Scholar
- 76.Song, J. J., et al. (2003). The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nature Structural Biology, 10, 1026–1032.CrossRefGoogle Scholar
- 77.Klein, M., Chandradoss, S. D., Depken, M., & Joo, C. (2017). Why Argonaute is needed to make microRNA target search fast and reliable. Seminars in Cell and Developmental Biology, 65, 20–28.CrossRefGoogle Scholar
- 78.Salomon, W. E., Jolly, S. M., Moore, M. J., Zamore, P. D., & Serebrov, V. (2015). Single-molecule imaging reveals that Argonaute reshapes the binding properties of its nucleic acid guides. Cell, 162, 84–95.CrossRefGoogle Scholar
- 79.Chandradoss, S. D., Schirle, N. T., Szczepaniak, M., MacRae, I. J., & Joo, C. (2015). A dynamic search process underlies microRNA targeting. Cell, 162, 96–107.CrossRefGoogle Scholar
- 80.Elkayam, E., et al. (2012). The structure of human argonaute-2 in complex with miR-20a. Cell, 150, 100–110.CrossRefGoogle Scholar
- 81.Nakanishi, K., Weinberg, D. E., Bartel, D. P., & Patel, D. J. (2012). Structure of yeast Argonaute with guide RNA. Nature, 486, 368–374.ADSCrossRefGoogle Scholar
- 82.Lai, E. C. (2002). Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genetics, 30, 363–364.CrossRefGoogle Scholar
- 83.Berg, O. G., Winter, R. B., & von Hippel, P. H. (1981). Diffusion-driven mechanisms of protein translocation on nucleic acids. Biochemistry, 20, 6929–6948.CrossRefGoogle Scholar
- 84.Riggs, A. D., Bourgeois, S., & Cohn, M. (1970). The lac represspr-operator interaction III. Kinetic studies. The Journal of Molecular Biology, 53, 401–417.CrossRefGoogle Scholar
- 85.von Hippel, P. H., & Berg, O. G. (1989). Facilitated target location in biological systems. The Journal of Biological Chemistry, 264, 675–678.Google Scholar
- 86.Mirny, L., et al. (2009). How a protein searches for its site on DNA: The mechanism of facilitated diffusion. Journal of Physics A: Mathematical and Theoretical, 42ADSMathSciNetzbMATHCrossRefGoogle Scholar
- 87.Slutsky, M., & Mirny, L. A. (2004). Kinetics of protein-DNA interaction: Facilitated target location in sequence-dependent potential. The Biophysical Journal, 87, 4021–4035.ADSCrossRefGoogle Scholar
- 88.Gerland, U., Moroz, J. D., & Hwa, T. (2002). Physical constraints and functional characterists of transcription factor-DNA interaction. Proceedings of the National Academy of Sciences of the United States of America, 99, 12015–12020.ADSCrossRefGoogle Scholar
- 89.Kong, M., & Van Houten, B. (2017). Rad4 recognition-at-a-distance: Physical basis of conformation-specific anomalous diffusion of DNA repair proteins. Progress in Biophysics & Molecular Biology, 127, 93–104.CrossRefGoogle Scholar
- 90.Chiu, Y.-L., & Rana, T. M. (2002). RNAi in human cells. Molecular Cell, 10, 549–561.CrossRefGoogle Scholar
- 91.Doench, J. G., Petersen, C. P., & Sharp, P. A. (2003). siRNAs can function as miRNAs. Genes & Development, 17, 438–442.CrossRefGoogle Scholar
- 92.Hutvagner, G., & Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297, 2056–2060.ADSCrossRefGoogle Scholar
- 93.Bartel, D. P. (2009). MicroRNAs: Target recognition and regulatory functions. Cell, 136, 215–233.CrossRefGoogle Scholar
- 94.Krek, A., et al. (2005). Combinatorial microRNA target predictions. Nature Genetics, 37, 495–500.CrossRefGoogle Scholar
- 95.Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15–20.CrossRefGoogle Scholar
- 96.Lim, L. P., et al. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433, 769–773.ADSCrossRefGoogle Scholar
- 97.Faehnle, C. R., Elkayam, E., Haase, A. D., Hannon, G. J., & Joshua-Tor, L. (2013). The making of a slicer: Activation of human Argonaute-1. Cell Reports, 3, 1901–1909.CrossRefGoogle Scholar
- 98.Nakanishi, K., et al. (2013). Eukaryote-specific insertion elements control human ARGONAUTE slicer activity. Cell Reports, 3, 1893–1900.CrossRefGoogle Scholar
- 99.Jo, M. H., et al. (2015). Human Argonaute 2 has diverse reaction pathways on target RNAs. Molecular Cell, 59, 117–124.CrossRefGoogle Scholar
- 100.Wee, L. M., Flores-Jasso, C. F., Salomon, W. E., & Zamore, P. D. (2012). Argonaute divides its RNA guide into domains with distinct functions and RNA-binding properties. Cell, 151, 1055–1067.CrossRefGoogle Scholar
- 101.Sasaki, H. M., & Tomari, Y. (2012). The true core of RNA silencing revealed. Nature Structural & Molecular Biology, 19, 657–660.CrossRefGoogle Scholar
- 102.Zander, A., Holzmeister, P., Klose, D., Tinnefeld, P., & Grohmann, D. (2014). Single-molecule FRET supports the two-state model of Argonaute action. RNA Biology, 11, 45–56.CrossRefGoogle Scholar
- 103.Herschlag, D. (1991). Implications of ribozyme kinetics for targeting the cleavage of specific RNA molecules in vivo: More isn’t always better. Proceedings of the National Academy of Sciences of the United States of America, 88, 6921–6925.ADSCrossRefGoogle Scholar
- 104.Deerberg, A., Willkomm, S., & Restle, T. (2013). Minimal mechanistic model of siRNA-dependent target RNA slicing by recombinant human Argonaute 2 protein. Proceedings of the National Academy of Sciences of the United States of America, 110, 17850–17855.ADSCrossRefGoogle Scholar
- 105.Bofill-De Ros, X., & Gu, S. (2016). Guidelines for the optimal design of miRNA-based shRNAs. Methods, 103, 157–166.CrossRefGoogle Scholar
- 106.Seitz, H., Tushir, J. S., & Zamore, P. D. (2011). A 5′-uridine amplifies miRNA/miRNA* asymmetry in Drosophila by promoting RNA-induced silencing complex formation. Silence, 2, 4.CrossRefGoogle Scholar
- 107.Mi, S., et al. (2008). Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell, 133, 116–127.CrossRefGoogle Scholar
- 108.Schirle, N. T., Sheu-Gruttadauria, J., Chandradoss, S. D., Joo, C., & MacRae, I. J. (2015). Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets. Elife, 4Google Scholar
- 109.Casey, M. C., Kerin, M. J., Brown, J. A., & Sweeney, K. J. (2015). Evolution of a research field-a micro (RNA) example. PeerJ, 3, e829.CrossRefGoogle Scholar
- 110.Ragunathan, K., Liu, C., & Ha, T. (2012). RecA filament sliding on DNA facilitates homology search. Elife, 1, e00067.CrossRefGoogle Scholar
- 111.Qi, Z., et al. (2015). DNA sequence alignment by microhomology sampling during homologous recombination. Cell, 160, 856–869.CrossRefGoogle Scholar
- 112.Shvets, A. A., & Kolomeisky, A. B. (2017). Mechanism of genome interrogation: How CRISPR RNA-guided Cas9 proteins locate specific targets on DNA. The Biophysical Journal, 113, 1416–1424.ADSCrossRefGoogle Scholar
- 113.Sternberg, S. H., LaFrance, B., Kaplan, M., & Doudna, J. A. (2015). Conformational control of DNA target cleavage by CRISPR-Cas9. Nature, 527, 110–113.ADSCrossRefGoogle Scholar
- 114.Westra, E. R., et al. (2013). Type I-E CRISPR-cas systems discriminate target from non-target DNA through base pairing-independent PAM recognition. PLOS Genetics, 9, e1003742.CrossRefGoogle Scholar