Jessica Brown

Associate Professor

451 Stepan Chemistry
Notre Dame, IN 46556
+1 574-631-6486

Research Areas

  • Biochemistry

Research Specialties

  • Life Processes
  • Measurement

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Year Title
2022-present Associate Professor, University of Notre Dame
2016-2022 Clare Boothe Luce Assistant Professor, University of Notre Dame
2011-2016 Postdoctoral Fellow, Yale University and Howard Hughes Medical Institute
2010 Ph.D. in Biochemistry, The Ohio State University
2005 B.S. in Chemistry and Biological Sciences, Wright State University

Selected Awards

2014-2019   NIH Pathway to Independence Award (K99/R00)

2012-2014   American Cancer Society Postdoctoral Fellowship

2010                 OSU Presidential Fellowship

2008-2010   American Heart Association Predoctoral Fellowship

Research Interests

Structural, Biochemical & Cellular Roles of RNA Triple Helices

RNA structure is largely viewed as being single stranded or double stranded, although triple-stranded RNA structures were deduced to form in test tubes over 60 years ago. Despite this early discovery of RNA triple helices, only three examples from eukaryotic cellular RNAs have been validated by three-dimensional structures. The long-term goal of the Brown laboratory is to understand the structural, biochemical, and cellular roles of RNA triple helices using the MALAT1 triple helix as a model. This triple helix forms at the 3' end of the long noncoding RNA, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). This triple helix forms when a U-rich internal loop of a stem-loop structure binds and sequesters a downstream 3'-terminal A-rich tract. This unique triple-helical structure, composed of nine U•A-U triples separated by a C+•G-C triple and C-G doublet, protects MALAT1 from an uncharacterized rapid nuclear RNA pathway.

The fundamental structural and biochemical properties of RNA triple helices remain to be rigorously characterized. The Brown laboratory is interested in several key questions. How do proteins and small molecules bind specifically to an RNA triple helix? Is there an undiscovered class of triple-stranded RNA binding proteins? How does the cell degrade a highly stable triple-helical RNA structure? What is the relative stability of canonical (U•A-U and C•G-C) versus non-canonical base triples? Can successive non-canonical base triples form a stable triple helix? What are the structural parameters of an ideal RNA triple helix? What is the folding pathway of an RNA triple helix? What other RNA triple helices exist in mammalian cells? Can we create experimental tools to establish the "triplexome?" To investigate these questions, we are currently using a variety of approaches, including X-ray crystallography, single-particle cryo-EM, cell-based assays, molecular biology, classical biochemistry and high-throughput methods.

Studying the MALAT1 triple helix will advance our understanding of cancer. MALAT1 is upregulated in multiple types of cancer and promotes tumor growth by affecting proliferation, invasion, and metastasis. Importantly, the region of MALAT1 that is sufficient to induce oncogenic activities includes the triple helix. Our work shows that the MALAT1 triple helix is required for MALAT1 accumulation; therefore, we are currently exploring whether the triple helix plays a direct role in mediating oncogenic activities beyond its function as an RNA stability element.

Positions are available for talented graduate students and postdoctoral researchers.

Selected Publications

  • Shivakumar, K. M.; Mahendran, G. and Brown, J. A. "Locked Nucleic Acid Oligonucleotides Facilitate RNA•LNA-RNA Triple-Helix Formation and Reduce MALAT1 Levels" 2024 International Journal of Molecular Sciences, 25 (3), 1630. DOI: 10.3390/ijms25031630.
  • Breger, K.; Kunkler, C. N.; O'Leary, N. J.; Hulewicz, J. P. and Brown, J. A. "Ghost Authors Revealed: The Structure and Function of Human N6-Methyladenosine RNA Methyltransferases" 2024 Wiley Interdisciplinary Reviews-RNA, 15 (1), e1810. DOI: 10.1002/wrna.1810.
  • Breger, K. and Brown, J. A. "Elucidating the Kinetic Mechanism of Human METTL16" 2022 Biochemistry, 62 (2), pp.494-506. DOI: 10.1021/acs.biochem.2c00601.
  • Alfonzo, J. D.; Brown, J. A.; Byers, P. H.; Cheung, V. G.; Maraia, R. J. and Ross, R. L. "A Call for Direct Sequencing of Full-Length RNAs to Identify all Modifications Comment" 2021 Nature Genetics, 53 (8), pp.1113-1116. DOI: 10.1038/s41588-021-00903-1.
  • Wang, M. C.; McCown, P. J.; Schiefelbein, G. E. and Brown, J. A. "Secondary Structural Model of MALAT1 Becomes Unstructured in Chronic Myeloid Leukemia and Undergoes Structural Rearrangement in Cervical Cancer" 2021 Non-Coding RNA, 7 (1), 6. DOI: 10.3390/ncrna7010006.
  • McCown, P. J.; Ruszkowska, A.; Kunkler, C. N.; Breger, K.; Hulewicz, J. P.; Wang, M. C.; Springer, N. A. and Brown, J. A. "Naturally Occurring Modified Ribonucleosides" 2020 Wiley Interdisciplinary Reviews-RNA, 11 (5), e1595. DOI: 10.1002/wrna.1595.