Professor & Chair, Department of Pharmaceutical Sciences
School of Pharmacy & Pharmaceutical Sciences

Professor, Chemistry
School of Physical Sciences

Member, Chao Family Comprehensive Cancer Center

Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Member, Institute for Genomics and Bioinformatics

RNA biology and chemistry

Luptak Research Group Website

1992-1996 Benjamin Franklin Scholar
2010 Pew Scholar
2020 Guggenheim Fellow
2021 W. M. Keck Foundation grantee

Research Fellow, Massachusetts General Hospital & Harvard Medical School 2002-2007

RNAs are remarkable as both information carriers and structured functional macromolecules. Beyond their well-known role in the information transfer between DNA and proteins, RNAs act as catalysts (ribozymes) in many cellular processes such as protein synthesis, splicing, and tRNA maturation. In addition, RNA can fold to form small-molecule recognition elements (riboswitches) that regulate gene expression. It is clear that RNA structure and regulation is critical to a wide variety of cellular events, but the complexity of regulatory mechanisms is only now beginning to be appreciated.

This duality of function makes RNAs and their chemical analogs ideal for in vitro selection and evolution experiments. In vitro selection is a powerful tool for rapid cell-free identification of specific binders or efficient catalysts from very diverse synthetic or genomic libraries, with complexities of up to about 10E16. Aptamers, RNAs with high binding affinity and specificity, are readily isolated and can be evolved further to improve or alter their function. For example, they have been developed to bind a large variety of small molecule targets, to act as drugs that bind proteins and cells in a tissue-specific manner, and to deliver cargoes to those cells. Similarly, ribozymes have been evolved in vitro to accelerate a wide variety of chemical reactions.

We explore the biology and chemistry of RNA by utilizing in vitro selection techniques and structure-based bioinformatics to search for new catalytic RNAs in a variety of genomes. Through these RNAs, we look for novel modes of cell regulation. Another way in which we combine the study of RNA biology and chemistry is to use synthetic libraries to select aptamers and ribozymes with designed characteristics. Of particular interest is the selection of fluorogenic molecules that we will use to study RNA in live cells with hitherto unprecedented spatial and temporal resolution. To facilitate the selection process we are developing novel fluorescence-based methods to display and isolate fluorogenic nucleic acids.

Links to Course Web Pages
Chem/PharmSci 223. Bio Macromolecules

Patent
RIBOZYME WITH tRNA SYNTHETASE ACTIVITY AND METHODS OF MANUFACTURING AND USING THE SAME

Claire C. Chen, Joseph Han, Carlene A. Chinn, Xiang Li, Mehran Nikan, Marie Myszka, Liqi Tong, Timothy W. Bredy, Marcelo A. Wood, Andrej Lupták (2024)
Inhibition of Cpeb3 ribozyme elevates CPEB3 protein expression and polyadenylation of its target mRNAs, and enhances object location memory.
eLife 13:e90116

Ng KK, Cole KH, Halbers LH, Chen C, Barhoosh AA, Reid-McLaughlin E, Metcalfe M, Kent AD, Steward O, Lupták A, Prescher JA (2022)
A modular platform for bioluminescent RNA tracking
bioRxiv 2022.07.02.498144; doi: https://doi.org/10.1101/2022.07.02.498144

Kent AD, Yang LL, Lee IA, Lupták A (2022)
Pyrophosphate-Mediated Repair of Damaged and Mismatched RNA by a Polymerase Ribozyme
bioRxiv 2022.11.01.514781; doi: https://doi.org/10.1101/2022.11.01.514781

Cole, KH, Mogannam, K, Lupták A (2023)
Choreography of a self-splicing ribozyme (News & Views).
Nature Catalysis 6, 291–293

Cole KH, Bouin A, Ruiz C, Semler BL, Inlay MA, Lupták A. (2022)
Single-tube collection and nucleic acid analysis of clinical samples for SARS-CoV-2 saliva testing.
Scientific Reports 12:3951

Peng H, Latifi B, Müller S, Lupták A. Chen IA. (2021)
Self-cleaving ribozymes: substrate specificity and synthetic biology applications.
RSC Chem Biol 2:1370-1383

Chen CC, Lupták A. (2021)
Hunting for human ribozymes (News & Views).
Nature Chemical Biology 17, 507–508

Chizzolini F, Kent A, Passalacqua LFM, Lupták A. (2021)
Enzymatic RNA production from NTPs synthesized from nucleosides and trimetaphosphate.
ChemBioChem 22: 2098–2101

Passalacqua LFM, Dingilian AI, Lupták A. (2020)
Single-pass transcription by T7 RNA polymerase.
RNA 26: 2062-2071

Rotstan KA, Abdelsayed MM, Passalacqua LFM, Chizzolini F, Sudarshan K, Chamberlin AR, Míšek J, Lupták A. (2020)
Regulation of mRNA translation by a photoriboswitch.
eLife 9:e51737

Chizzolini F, Passalacqua LFM, Oumais M, Dingilian AI, Szostak JW, Lupták A (2020)
Large Phenotypic Enhancement of Structured Random RNA Pools.
J Am Chem Soc 142, 4, 1941-1951.

Passalacqua LFM, Lupták A. (2021)
Co-transcriptional Analysis of Self-Cleaving Ribozymes and Their Ligand Dependence.
In: Scarborough R.J., Gatignol A. (eds) Ribozymes.
Methods in Molecular Biology, vol 2167

Cole, KH and Lupták, A (2019)
High-throughput methods in aptamer discovery and analysis.
Methods in Enzymology 621:329-346

Webb, CH and Lupták, A. (2018)
Kinetic Parameters of Trans-scission by Extended HDV-like Ribozymes and the Prospect for the Discovery of Genomic Trans-cleaving RNAs.
Biochemistry 6;57(9):1440-1450

Burke, CR and Lupták, A. (2018)
DNA synthesis from diphosphate substrates by DNA polymerases.
PNAS 115(5): 980-985.

Passalacqua LFM, Jimenez RM, Fong JY, Luptak A. (2017)
Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus-like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene Product.
Biochemistry 56: 6006-6014.

Abdelsayed, MM; Ho, BT; Vu, MMK; Polanco, J; Spitale, RC; Lupták, A. (2017) Multiplex aptamer discovery through Apta-Seq and its application to ATP aptamers derived from human-genomic SELEX.
ACS Chem Biol 12 (8): 2149–2156

Webb CH, Nguyen D, Myszka M, Lupták A. (2016)
Topological constraints of structural elements in regulation of catalytic activity in HDV-like self-cleaving ribozymes.
Sci Rep. 6:28179.

Manuel, G, Lupták, A, Corn, RM. (2016)
A microwell–printing fabrication strategy for the on-chip templated biosynthesis of protein microarrays for surface plasmon resonance imaging.
J Phys Chem C 120:20984-20990

Rampášek L, Jimenez RM, Lupták A, Vinar T, Brejová B. (2016)
RNA motif search with data-driven element ordering.
BMC Bioinformatics 17:216.

Kozlyuk N, Sengupta S, Lupták A, Martin RW. (2016)
In situ NMR measurement of macromolecule-bound metal ion concentrations.
J Biomol NMR 64(4):269-273.

Pobanz K and Lupták A (2016)
Improving the odds: Influence of starting pools on in vitro selection outcomes.
Methods 106:14-20

Jimenez RM, Polanco JA, Lupták A. (2015)
Chemistry and Biology of Self-Cleaving Ribozymes.
Trends in Biochemical Sciences 40(11):648-61.

Long A, Liti G, Luptak A, Tenaillon O. (2015)
Elucidating the molecular architecture of adaptation via evolve and resequence experiments.
Nature Reviews Genetics 16(10):567-82.

Burke, CR and Lupták, A. (2015) Catalytic properties of RNA. in Discoveries in modern science: Exploration, invention, technology. Trefil, J. (ed.)
Macmillan reference.

Ho, B., Polanco, J., Jimenez, R.M. & Lupták, A. (2014) Discovering human RNA aptamers by structure-based bioinformatics and genome-based in vitro selection.
Methods in Enzymol. 549:29-46.

Riccitelli, N.J., Delwart, E. & Lupták, A. (2014) Identification of minimal HDV-like ribozymes with unique divalent metal ion dependence in the human microbiome.
Biochemistry 53: 16-16-1626.

Riccitelli, N.J. & Lupták, A. (2013) HDV family of self-cleaving ribozymes.
Prog Mol Biol Transl Sci. 120:123-71.

Vu, MMK, Jameson, NE, Masuda, SJ, Lin, D, Larralde-Ridaura, R & Lupták, A. (2012) Convergent evolution of adenosine aptamers spanning bacterial, human, and random sequences revealed by structure-based bioinformatics and genomic SELEX.
Chemistry & Biology 19:1247-54.

Hammann C, Lupták A, Perreault J, de la Peña M. (2012) The uniquitous hammerhead ribozyme.
RNA 18(5): 871-85.

Jimenez RM, Rampášek L, Brejová B, Vinar T, Lupták A. (2012) Discovery of RNA Motifs Using a Computational Pipeline that Allows Insertions in Paired Regions and Filtering of Candidate Sequences.
Methods Mol Biol. 848:145-58.

Jimenez RM, Lupták A. (2012) Structure-based search and in vitro analysis of self-cleaving ribozymes.
Methods Mol Biol. 848:131-43.

Xiao Z, Levy-Nissenbaum E, Alexis F, Lupták A, Teply BA, Chan JM, Shi J, Digga E, Cheng J, Langer R, Farokhzad OC. (2012) Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection.
ACS Nano 6(1):696-704.

Ruminski DJ, Webb C-HT, Riccitelli NJ, Lupták A. (2011) Processing and translation initiation of non-long terminal repeat retrotransposons by hepatitis delta virus (HDV)-like self-cleaving ribozymes.
J Biol Chem 286(48):41286-95.

Webb C-H T and Lupták A. (2011) RNA Families: HDV-like Self-cleaving Ribozymes.
RNA Biology, 8(5):719-727.

Trevino S, Zhang N, Elenko M, Lupták A and Szostak JW. (2011) Evolution of functional nucleic acids in the presence of non-heritable backbone heterogeneity.
PNAS 108(33):13492-7.

Iuliana E. Sendroiu, Lida K. Gifford, Andrej Lupták, and Robert M. Corn. (2011) Ultrasensitive DNA Microarray Biosensing via in Situ RNA Transcription-Based Amplification and Nanoparticle-Enhanced SPR Imaging.
J Am Chem Soc, 133 (12), 4271–4273

Jimenez RM, Delwart E, and Lupták A. (2011) Structure-based search reveals hammerhead ribozymes in the human microbiome.
J Biol Chem 286(10):7737-43.
Paper of the week.
Best of JBC 2011.

Gifford L, Sendroiu I, Corn R, Lupták A. (2010) Attomole Detection of Mesophilic DNA Polymerase Products by Nanoparticle-Enhanced SPR Imaging on Glassified Gold Surfaces.
J Am Chem Soc, 132(27): 9265-9267.

Riccitelli NJ, Lupták A. (2010) Computational discovery of folded RNA domains in genomes and in vitro selected libraries.
Methods 52:133-140.

Webb C-HT, Riccitelli NJ, Ruminski DJ and Lupták A. (2009) Widespread occurrence of self-cleaving ribozymes.
Science 326:953

Luptak A, Szostak JW. Mammalian self-cleaving ribozymes. in Ribozymes and RNA Catalysis, eds D. Lilley and F. Eckstein, 2008.

Monnard PA, Luptak A, Deamer DW. (2007) Models of primitive cellular life: polymerases and templates in liposomes. Philos Trans R Soc Lond B Biol Sci. 362(1486):1741-50.

Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. (2006) Science. 313(5794):1788-92.

Luptak A, Doudna JA. Distinct sites of phosphorothioate substitution interfere with folding and splicing of the Anabaena group I intron. (2004) Nucleic Acids Res. 32(7):2272-80.

Luptak A, Ferre-D'Amare AR, Zhou K, Zilm KW, Doudna JA. Direct pK(a) measurement of the active-site cytosine in a genomic hepatitis delta virus ribozyme. (2001) J Am Chem Soc. 123(35):8447-52.

NASA Exobiology "High-Energy Phosphate In Early Genome Replication And Maintenance"

NASA ICAR "Bringing RNA to Life – Emergence of Biocatalysis"

W. M. Keck Foundation "Tracing the synaptic transcriptome in live animals with luminescent RNAs"

UC Cancer Research Coordinating Committee "Role of cytoplasmic polyadenylation element binding protein 3 (CPEB3) ribozyme in cancer"

<A HREF="http://www.rnasociety.org/"> RNA Society

<A HREF='http://www.asbmb.org/'> ASBMB

<A HREF='http://www.aaas.org//'> AAAS

<A HREF ="http://www.acs.org/content/acs/en.html"> American Chemical Society

Cellular and Molecular Biosciences

Chemical Biology

Chemistry

Medicinal Chemistry and Pharmacology

Pharmacological Sciences

Link to this profile
https://faculty.uci.edu/profile/?facultyId=5448

Last updated
02/06/2024