Ewan K.S. McRae

Ewan K.S. McRae, PhD

Assistant Professor of Cardiovascular Sciences, Academic Institute
Assistant Member, Research Institute
Houston Methodist
Weill Cornell Medical College

McRae lab

Description of Research

The McRae lab is currently funded by a 5-year CPRIT recruitment grant to perform structure-based design of RNA therapeutics.

RNA therapeutics are emerging as a new way of targeting previously un-druggable therapeutic targets, and their full potential has yet to be realized. The focus thus far has been on RNA sequence, whereas next generation therapies will also utilize RNA structure. Current mRNA therapy design has optimized 5’ and 3’ untranslated regions (UTRS) as well as the coding sequence to maximize the translational output of mRNA. The 5’ and 3’ UTR sequences have been borrowed from naturally occurring sequences that have abundant translational output, resulting in an mRNA therapeutic that is ubiquitously expressed wherever the mRNA encounters translational machinery. However, key property of 5’ and 3’ UTRs is their complex 3D structure that allows them to regulate protein expression in a tightly controlled manner. Harnessing the full regulatory power of 5’ and 3’ UTRs for translational control of mRNA therapeutics would allow for expression of the mRNA payload only in the correct cellular context and reduce off-target effects. Achieving this regulatory specificity requires an understanding of RNA structural biology and the molecular interactions that govern the structure of 5’ and 3’ UTRs. Our research group uses cryo-EM structure determination and the design principles from the RNA origami method to modify RNA structures to improve the currently used 5’ and 3’ UTRs of mRNA therapies. By exploiting the cancer cell environment to enable cell state-specific expression and stabilization of the mRNA we hope to improve the efficacy of mRNA therapies for immunizing against and treating cancers.


An RNA origami robot that traps and releases a fluorescent aptamer
Vallina, NS, McRae, EKS, Geary, C & Andersen, ES 2024, , Science Advances, vol. 10, no. 12, eadk1250, pp. eadk1250. https://doi.org/10.1126/sciadv.adk1250

Cryo-EM structure and functional landscape of an RNA polymerase ribozyme
McRae, EKS, Wan, CJK, Kristoffersen, EL, Hansen, K, Gianni, E, Gallego, I, Curran, JF, Attwater, J, Holliger, P & Andersen, ES 2024, , Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 3, e2313332121, pp. e2313332121. https://doi.org/10.1073/pnas.2313332121

RNA origami scaffolds facilitate cryo-EM characterization of a Broccoli-Pepper aptamer FRET pair
Sampedro Vallina, N, McRae, EKS, Hansen, BK, Boussebayle, A & Andersen, ES 2023, , Nucleic Acids Research, vol. 51, no. 9, pp. 4613-4624. https://doi.org/10.1093/nar/gkad224

Structure, folding and flexibility of co-transcriptional RNA origami
McRae, EKS, Rasmussen, HØ, Liu, J, Bøggild, A, Nguyen, MTA, Sampedro Vallina, N, Boesen, T, Pedersen, JS, Ren, G, Geary, C & Andersen, ES 2023, , Nature Nanotechnology, vol. 18, no. 7, pp. 808-817. https://doi.org/10.1038/s41565-023-01321-6

RNA target highlights in CASP15: Evaluation of predicted models by structure providers
Kretsch, RC, Andersen, ES, Bujnicki, JM, Chiu, W, Das, R, Luo, B, Masquida, B, McRae, EKS, Schroeder, GM, Su, Z, Wedekind, JE, Xu, L, Zhang, K, Zheludev, IN, Moult, J & Kryshtafovych, A 2023, , Proteins: Structure, Function and Bioinformatics, vol. 91, no. 12, pp. 1600-1615. https://doi.org/10.1002/prot.26550

An RNA Paranemic Crossover Triangle as A 3D Module for Cotranscriptional Nanoassembly
Sampedro Vallina, N, McRae, EKS, Geary, C & Andersen, ES 2023, , Small, vol. 19, no. 13, 2204651, pp. e2204651. https://doi.org/10.1002/smll.202204651

RNA origami design tools enable cotranscriptional folding of kilobase-sized nanoscaffolds
Geary, C, Grossi, G, McRae, EKS, Rothemund, PWK & Andersen, ES 2021, , Nature Chemistry, vol. 13, no. 6, pp. 549-558. https://doi.org/10.1038/s41557-021-00679-1

Monitoring Enzymatic RNA G-Quadruplex Unwinding Activities by Nuclease Sensitivity and Reverse Transcription Stop Assays
McRae, EKS, Dupas, SJ, Atefi, N & McKenna, SA 2021, . in Methods in Molecular Biology. Methods in Molecular Biology, vol. 2209, Humana Press, pp. 163-173. https://doi.org/10.1007/978-1-0716-0935-4_11

An RNA guanine quadruplex regulated pathway to TRAIL-sensitization by DDX21
McRae, EKS, Dupas, SJ, Booy, EP, Piragasam, RS, Fahlman, RP & Mckenna, SA 2020, , RNA, vol. 26, no. 1, pp. 44-57. https://doi.org/10.1261/rna.072199.119

2D saturation transfer difference nmr for determination of protein binding sites on rna guanine quadruplexes
McRae, EKS, Davidson, DE & McKenna, SA 2020, . in Methods in Molecular Biology. Methods in Molecular Biology, vol. 2161, Humana Press, pp. 101-113. https://doi.org/10.1007/978-1-0716-0680-3_9

Binding and photodynamic action of the cationic zinc phthalocyanines with different types of DNA toward understanding of their cancer therapy activity
McRae, EKS, Nevonen, DE, McKenna, SA & Nemykin, VN 2019, , Journal of Inorganic Biochemistry, vol. 199, 110793. https://doi.org/10.1016/j.jinorgbio.2019.110793

Comprehensive analysis of the BC200 ribonucleoprotein reveals a reciprocal regulatory function with CSDE1/UNR
Booy, EP, McRae, EKS, Ezzati, P, Choi, T, Gussakovsky, D & McKenna, SA 2018, , Nucleic Acids Research, vol. 46, no. 21, pp. 11575-11591. https://doi.org/10.1093/nar/gky860

Insights into the RNA quadruplex binding specificity of DDX21
McRae, EKS, Davidson, DE, Dupas, SJ & McKenna, SA 2018, , Biochimica et Biophysica Acta - General Subjects, vol. 1862, no. 9, pp. 1973-1979. https://doi.org/10.1016/j.bbagen.2018.06.009

Structure and hydrodynamics of a DNA G-quadruplex with a cytosine bulge
Meier, M, Moya-Torres, A, Krahn, NJ, McDougall, MD, Orriss, GL, McRae, EKS, Booy, EP, McEleney, K, Patel, TR, McKenna, SA & Stetefeld, J 2018, , Nucleic Acids Research, vol. 46, no. 10, pp. 5319-5331. https://doi.org/10.1093/nar/gky307

The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation
Booy, EP, McRae, EKS, Koul, A, Lin, F & McKenna, SA 2017, , Molecular Cancer, vol. 16, no. 1, 109. https://doi.org/10.1186/s12943-017-0679-7

Human DDX21 binds and unwinds RNA guanine quadruplexes
McRae, EKS, Booy, EP, Moya-Torres, A, Ezzati, P, Stetefeld, J & McKenna, SA 2017, , Nucleic Acids Research, vol. 45, no. 11, pp. 6656-6668. https://doi.org/10.1093/nar/gkx380

Impact of G-quadruplex loop conformation in the PITX1 mRNA on protein and small molecule interaction
Ariyo, EO, Booy, EP, Dzananovic, E, McRae, EK, Meier, M, McEleney, K, Stetefeld, J & McKenna, SA 2017, , Biochemical and Biophysical Research Communications, vol. 487, no. 2, pp. 274-280. https://doi.org/10.1016/j.bbrc.2017.04.049

On characterizing the interactions between proteins and guanine quadruplex structures of nucleic acids
McRae, EKS, Booy, EP, Padilla-Meier, GP & McKenna, SA 2017, , Journal of Nucleic Acids, vol. 2017, 9675348. https://doi.org/10.1155/2017/9675348

RNA helicase associated with AU-rich element (RHAU/DHX36) interacts with the 3'-tail of the long non-coding RNA BC200 (BCYRN1)
Booy, EP, McRae, EKS, Howard, R, Deo, SR, Ariyo, EO, Dzananovic, E, Meier, M, Stetefeld, J & McKenna, SA 2016, , Journal of Biological Chemistry, vol. 291, no. 10, pp. 5355-5372. https://doi.org/10.1074/jbc.M115.711499

Biophysical characterization of G-quadruplex recognition in the PITX1 mRNA by the specificity domain of the helicase RHAU
Ariyo, EO, Booy, EP, Patel, TR, Dzananovic, E, McRae, EK, Meier, M, McEleney, K, Stetefeld, J & McKenna, SA 2015, , PLoS ONE, vol. 10, no. 12, e0144510. https://doi.org/10.1371/journal.pone.0144510