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MacRae, Ian
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MacRae, Ian

Faculty Member
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Positions

  • 2016 - Professor, Integrative Structural and Computational Biology (ISCB) , Scripps Research
  • 2007 - Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2013 - 2016 Associate Professor, Integrative Structural and Computational Biology (ISCB) , Scripps Research
  • 2007 - 2012 Assistant Professor, Molecular Biology , Scripps Research
Dr. Ian MacRae combines structural biology, biochemistry and cell biology to understand mechanisms of gene regulation by RNA interference.

Research Areas research areas

  • Alzheimer (UMLS)
  • Cancer (UMLS)
  • Heart Disease (UMLS)

Contact

  • macrae@scripps.edu

Websites

  • Ian J. MacRae, Ph.D.
  • MacRae Laboratory
  • Publications
  • Research
  • Teaching
  • Background
  • Contact
  • Identity
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Publications

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  • Publications without PubMed PMIDs

  • academic article

    • Ruijtenberg, S., Sonneveld, S., Cui, T. J., Logister, I., de Steenwinkel, D., Xiao, Y., Macrae, I. J., Joo, C., Tanenbaum, M. E. mRNA structural dynamics shape Argonaute-target interactions Nature Structural & Molecular Biology  2020  DOI:10.1038/s41594-020-0461-1  PMID:32661421
    • Xiao, Y., Macrae, I. J. Robust differential microRNA targeting driven by supplementary interactions in vitro RNA  2020 26:162-174  DOI:10.1261/rna.072264.119  PMID:31732536  PMCID:PMC6961540
    • Sheu-Gruttadauria, J., Pawlica, P., Klum, S. M., Wang, S., Yario, T. A., Oakdale, N. T. S., Steitz, J. A., Macrae, I. J. Structural basis for target-directed microRNA degradation Molecular Cell  2019 75:1243-1255  DOI:10.1016/j.molcel.2019.06.019  PMID:31353209  PMCID:PMC6754277
    • Xiao, Y., Macrae, I. J. Toward a comprehensive view of microRNA biology Molecular Cell  2019 75:666-668  DOI:10.1016/j.molcel.2019.08.001  PMID:31442421
    • Sheu-Gruttadauria, J., Xiao, Y., Gebert, L. F. R., Macrae, I. J. Beyond the seed: structural basis for supplementary microRNA targeting by human Argonaute2 EMBO Journal  2019 38  DOI:10.15252/embj.2018101153  PMID:31268608  PMCID:PMC6600645
    • Chahal, J., Gebert, L. F. R., Gan, H. H., Camacho, E., Gunsalus, K. C., Macrae, I. J., Sagan, S. M. miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5 terminus Nucleic Acids Research  2019 47:5307-5324  DOI:10.1093/nar/gkz194  PMID:30941417  PMCID:PMC6547439
    • Foss, D. V., Schirle, N. T., Macrae, I. J., Pezacki, J. P. Structural insights into interactions between viral suppressor of RNA silencing protein p19 mutants and small RNAs FEBS Open Bio  2019 9:1042-1051  DOI:10.1002/2211-5463.12644  PMID:31021526  PMCID:PMC6551489
    • Ziv, O., Gabryelska, M. M., Lun, A. T. L., Gebert, L. F. R., Sheu-Gruttadauria, J., Meredith, L. W., Liu, Z. Y., Kwok, C. K., Qin, C. F., Macrae, I. J., Goodfellow, I., Marioni, J. C., et al. COMRADES determines in vivo RNA structures and interactions Nature Methods  2018 15:785-788  DOI:10.1038/s41592-018-0121-0  PMID:30202058  PMCID:PMC6168409
    • Sheu-Gruttadauria, J., Macrae, I. J. Phase transitions in the assembly and function of human miRISC Cell  2018 173:946-957  DOI:10.1016/j.cell.2018.02.051  PMID:29576456  PMCID:PMC5935535
    • Klum, S. M., Chandradoss, S. D., Schirle, N. T., Joo, C., Macrae, I. J. Helix-7 in Argonaute2 shapes the microRNA seed region for rapid target recognition EMBO Journal  2018 37:75-88  DOI:10.15252/embj.201796474  PMID:28939659  PMCID:PMC5753032
    • Sheu-Gruttadauria, J., MacRae, I. J. Structural foundations of RNA silencing by Argonaute Journal of Molecular Biology  2017 429:2619-2639  DOI:10.1016/j.jmb.2017.07.018  PMID:28757069  PMCID:PMC5576611
    • Schirle, N. T., Kinberger, G. A., Murray, H. F., Lima, W. F., Prakash, T. P., Macrae, I. J. Structural analysis of human Argonaute-2 bound to a modified siRNA guide Journal of the American Chemical Society  2016 138:8694-8697  DOI:10.1021/jacs.6b04454  PMID:27380263  PMCID:PMC4993527
    • Suter, S. R., Sheu-Gruttadauria, J., Schirle, N. T., Valenzuela, R., Ball-Jones, A. A., Onizuka, K., Macrae, I. J., Beal, P. A. Structure-guided control of siRNA off-target effects Journal of the American Chemical Society  2016 138:8667-8669  DOI:10.1021/jacs.6b06137  PMID:27387838  PMCID:PMC4962782
    • Wu, M. K., de Kock, L., Conwell, L. S., Stewart, C. J. R., King, B. R., Choong, C. S., Hussain, K., Sabbaghian, N., Macrae, I. J., Fabian, M. R., Foulkes, W. D. Functional characterization of multiple DICER1 mutations in an adolescent Endocrine-Related Cancer  2016 23:L1-L5  DOI:10.1530/erc-15-0460  PMID:26545620
    • Schirle, N. T., Sheu-Gruttadauria, J., Chandradoss, S. D., Joo, C., Macrae, I. J. Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets Elife  2015 4  DOI:10.7554/eLife.07646  PMID:26359634  PMCID:PMC4606517
    • Chandradoss, S. D., Schirle, N. T., Szczepaniak, M., Macrae, I. J., Joo, C. A dynamic search process underlies microRNA targeting Cell  2015 162:96-107  DOI:10.1016/j.cell.2015.06.032  PMID:26140593  PMCID:PMC4768356
    • Schirle, N. T., Sheu-Gruttadauria, J., Macrae, I. J. Structural basis for microRNA targeting Science  2014 346:608-613  DOI:10.1126/science.1258040  PMID:25359968  PMCID:PMC4313529
    • Xiong, X. P., Kurthkoti, K., Chang, K. Y., Lichinchi, G., De, N., Schneemann, A., Macrae, I. J., Rana, T. M., Perrimon, N., Zhou, R. Core small nuclear ribonucleoprotein particle splicing factor SmD1 modulates RNA interference in Drosophila Proceedings of the National Academy of Sciences of the United States of America  2013 110:16520-16525  DOI:10.1073/pnas.1315803110  PMID:24067655  PMCID:PMC3799365
    • Horman, S. R., Janas, M. M., Litterst, C., Wang, B., Macrae, I. J., Sever, M. J., Morrissey, D. V., Graves, P., Luo, B., Umesalma, S., Qi, H. H., Miraglia, L. J., et al. Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and upregulates translational repression of MicroRNA targets Molecular Cell  2013 50:356-367  DOI:10.1016/j.molce1.2013.03.015  PMID:23603119  PMCID:PMC3654076
    • De, N., Young, L., Lau, P. W., Meisner, N. C., Morrissey, D. V., Macrae, I. J. Highly complementary target RNAs promote release of guide RNAs from human Argonaute2 Molecular Cell  2013 50:344-355  DOI:10.1016/j.molcel.2013.04.001  PMID:23664376  PMCID:PMC3746828
    • Lau, P. W., Potter, C. S., Carragher, B., MacRae, I. J. DOLORS: versatile strategy for internal labeling and domain localization in electron microscopy Structure  2012 20:1995-2002  DOI:10.1016/j.str.2012.10.019  PMID:23217681  PMCID:PMC3535077
    • Bale, S., Julien, J. P., Bornholdt, Z. A., Kimberlin, C. R., Halfmann, P., Zandonatti, M. A., Kunert, J., Kroon, G. J. A., Kawaoka, Y., MacRae, I. J., Wilson, I. A., Saphire, E. O. Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism PLoS Pathogens  2012 8:e1002916  DOI:10.1371/journal.ppat.1002916  PMID:23028316  PMCID:PMC3441732
    • Schirle, N. T., MacRae, I. J. The crystal structure of human Argonaute2 Science  2012 336:1037-1040  DOI:10.1126/science.1221551  PMID:22539551  PMCID:PMC3521581
    • Pratt, A. J., Rambo, R. P., Lau, P. W., MacRae, I. J. Preparation and characterization of the extracellular domain of human Sid-1 PLoS One  2012 7:e33607  DOI:10.1371/journal.pone.0033607  PMID:22509261  PMCID:PMC3324469
    • Lau, P. W., Guiley, K. Z., De, N., Potter, C. S., Carragher, B., MacRae, I. J. The molecular architecture of human Dicer Nature Structural & Molecular Biology  2012 19:436-440  DOI:10.1038/nsmb.2268  PMID:22426548  PMCID:PMC3319852
    • Guiley, K. Z.*, Pratt, A. J.*, MacRae, I. J. Single-pot enzymatic synthesis of Dicer-substrate siRNAs Nucleic Acids Research  2012 40:e40  DOI:10.1093/nar/gkr1174  PMID:22189103  PMCID:PMC3299999 (* = equal contribution)
    • Hastie, K. M., Kimberlin, C. R., Zandonatti, M. A., MacRae, I. J., Saphire, E. O. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression Proceedings of the National Academy of Sciences of the United States of America  2011 108:2396-2401  DOI:10.1073/pnas.1016404108  PMID:21262835  PMCID:PMC3038715
    • De, N., Macrae, I. J. Purification and assembly of human Argonaute, Dicer, and TRBP complexes Methods in Molecular Biology  2011 725:107-119  DOI:10.1007/978-1-61779-046-1_8  PMID:21528450  PMCID:PMC3532949
    • Kimberlin, C. R., Bornholdt, Z. A., Li, S., Woods, V. L., MacRae, I. J., Saphire, E. O. Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune suppression Proceedings of the National Academy of Sciences of the United States of America  2010 107:314-319  DOI:10.1073/pnas.0910547107  PMID:20018665  PMCID:PMC2806767
    • Lau, P. W., Potter, C. S., Carragher, B., MacRae, I. J. Structure of the human Dicer-TRBP complex by electron microscopy Structure  2009 17:1326-1332  DOI:10.1016/j.str.2009.08.013  PMID:19836333  PMCID:PMC2880462
    • Pratt, A. J., MacRae, I. J. The RNA-induced silencing complex: A versatile gene-silencing machine Journal of Biological Chemistry  2009 284:17897-17901  DOI:10.1074/jbc.R900012200  PMID:19342379  PMCID:PMC2709356
    • Lau, P. W., MacRae, I. J. The molecular machines that mediate microRNA maturation Journal of Cellular and Molecular Medicine  2009 13:54-60  DOI:10.1111/j.1582-4934.2008.00520.x  PMID:19175700  PMCID:PMC3823036
    • Ma, E., MacRae, I. J., Kirsch, J. F., Doudna, J. A. Autoinhibition of human dicer by its internal helicase domain Journal of Molecular Biology  2008 380:237-243  DOI:10.1016/j.jmb.2008.05.005  PMID:18508075  PMCID:PMC2927216
    • MacRae, I. J., Ma, E., Zhou, M., Robinson, C. V., Doudna, J. A. In vitro reconstitution of the human RISC-loading complex Proceedings of the National Academy of Sciences of the United States of America  2008 105:512-517  DOI:10.1073/pnas.0710869105  PMID:18178619  PMCID:PMC2206567
    • MacRae, I. J., Doudna, J. A. An unusual case of pseudo-merohedral twinning in orthorhombic crystals of Dicer Acta Crystallographica Section D-Biological Crystallography  2007 63:993-999  DOI:10.1107/s0907444907036128  PMID:17704568
    • MacRae, I. J., Doudna, J. A. Ribonuclease revisited: structural insights into ribonuclease III family enzymes Current Opinion in Structural Biology  2007 17:138-145  DOI:10.1016/j.sbi.2006.12.002  PMID:17194582
    • MacRae, I. J., Zhou, K., Doudna, J. A. Structural determinants of RNA recognition and cleavage by Dicer Nature Structural & Molecular Biology  2007 14:934-940  DOI:10.1038/nsmb1293  PMID:17873886
    • MacRae, I. J., Zhou, K. H., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., Doudna, J. A. Structural basis for double-stranded RNA processing by Dicer Science  2006 311:195-198  DOI:10.1126/science.1121638  PMID:16410517
    • Macrae, I. J., Li, F., Zhou, K., Cande, W. Z., Doudna, J. A. Structure of Dicer and mechanistic implications for RNAi Cold Spring Harbor Symposia on Quantitative Biology  2006 71:73-80  DOI:10.1101/sqb.2006.71.042  PMID:17381283
    • Hanna, E., Ng, K. F., MacRae, I. J., Bley, C. J., Fisher, A. J., Segel, I. H. Kinetic and stability properties of Penicillium chrysogenum ATP sulfurylase missing the C-terminal regulatory domain Journal of Biological Chemistry  2004 279:4415-4424  DOI:10.1074/jbc.M311317200  PMID:14613928
    • MacRae, I. J., Segel, I. H., Fisher, A. J. Allosteric inhibition via R-state destabilization in ATP sulfurylase from Penicillium chrysogenum Nature Structural Biology  2002 9:945-949  DOI:10.1038/nsb868  PMID:12426581
    • Hanna, E., MacRae, I. J., Medina, D. C., Fisher, A. J., Segel, I. H. ATP sulfurylase from the hyperthermophilic chemolithotroph Aquifex aeolicus Archives of Biochemistry and Biophysics  2002 406:275-288  DOI:10.1016/s0003-9861(02)00428-9  PMID:12361716
    • Beynon, J. D., MacRae, I. J., Huston, S. L., Nelson, D. C., Segel, I. H., Fisher, A. J. Crystal structure of ATP sulfurylase from the bacterial symbiont of the hydrothermal vent tubeworm Riftia pachyptila Biochemistry  2001 40:14509-14517  DOI:10.1021/bi0156431  PMID:11724564
    • Medina, D. C., Hanna, E., MacRae, I. J., Fisher, A. J., Segel, I. H. Temperature effects on the allosteric transition of atp sulfurylase from penicillium chrysogenum Archives of Biochemistry and Biophysics  2001 393:51-60  DOI:10.1006/abbi.2001.2490  PMID:11516160
    • MacRae, I. J., Segel, I. H., Fisher, A. J. Crystal structure of atp sulfurylase from penicillium chrysogenum: Insights into the allosteric regulation of sulfate assimilation Biochemistry  2001 40:6795-6804  DOI:10.1021/bi010367w  PMID:11389593
    • MacRae, I. J., Hanna, E., Ho, J. D., Fisher, A. J., Segel, I. H. Induction of positive cooperativity by amino acid replacements within the C-terminal domain of penicillium chrysogenum ATP sulfurylase Journal of Biological Chemistry  2000 275:36303-36310  DOI:10.1074/jbc.M005992200  PMID:10956658
    • MacRae, I. J., Segel, I. H., Fisher, A. J. Crystal structure of adenosine 5 '-phosphosulfate kinase from Penicillium chrysogenum Biochemistry  2000 39:1613-1621  DOI:10.1021/bi9924157  PMID:10677210
    • MacRae, I. J., Segel, I. H. Adenosine 5 '-phosphosulfate (APS) kinase: Diagnosing the mechanism of substrate inhibition Archives of Biochemistry and Biophysics  1999 361:277-282  DOI:10.1006/abbi.1998.0993  PMID:9882457
    • MacRae, I. J., Rose, A. B., Segel, I. H. Adenosine 5 '-phosphosulfate kinase from Penicillium chrysogenum - site-directed mutagenesis at putative phosphoryl-accepting and ATP P-loop residues Journal of Biological Chemistry  1998 273:28583-28589  DOI:10.1074/jbc.273.44.28583  PMID:9786849
    • MacRae, I., Segel, I. H. ATP sulfurylase from filamentous fungi: which sulfonucleotide is the true allosteric effector? Archives of Biochemistry and Biophysics  1997 337:17-26  DOI:10.1006/abbi.1996.9751  PMID:8990263
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Research

research overview

  • RNA interference (RNAi) is a broad-spread mechanism of gene silencing that plays a fundamental role in many aspects of eukaryotic biology including viral defense, developmental timing, stem cell division, memory and learning. We are interested in understanding the molecular mechanisms underlying RNA interference (RNAi) and related RNA silencing processes. Our approach is to combine techniques in structural biology with biochemistry and cell biology in order to understand the mechanistic details of RNAi.

    On the molecular level RNAi is mediated by a family of ribonucleo-protein complexes called RNA-Induced Silencing Complexes (RISCs), which silence genes by mediating translational repression and degradation of targeted message RNAs. The versatility and power of RNAi arises from the fact that RISC can be programmed to target any nucleic acid sequence for silencing. RISC programming is therefore a critical cellular function, requiring the action of a specialized macromolecular assembly called the RISC-loading complex (RLC). Our current research is focused on illuminating the structure and catalytic mechanism of the RLC with the hope that this knowledge will facilitate the development of RNAi-based therapeutics for the treatment of human disease.
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Teaching

advisees

  • graduate advising relationship

    • Anzelon, Todd, Ph.D.  candidate, 2017 -
    • Madhavan, Aparajita, Ph.D.  candidate, 2016 -
    • Xiao, Yao, Ph.D.  candidate, 2016 -
    • Gruttadauria, Jessica Sheu, Ph.D.  candidate, 2013 - 2018
    • Klum, Shannon, Ph.D.  candidate, 2014 - 2018
    • Schirle Oakdale, Nicole, Ph.D.  candidate, 2012 - 2015
    • Pratt, Ashley J, Ph.D.  candidate, 2008 - 2012
    • Lau, Pick-Wei, Ph.D.  candidate, 2007 - 2011
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Background

education and training

  • Ph.D. in Molecular & Cellular Biology, University of California, Davis 2002
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Contact

full name

  • Ian John MacRae

geographic location

  • Scripps California 
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Identity

ORCID iD

  • ORCID iD http://orcid.org/0000-0002-5112-0294

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