Clare Boothe Luce Assistant Professor of Chemistry & Biochemistry at the University of Notre Dame
University of Notre Dame
RNA structure is largely viewed as being single stranded or double stranded, although triple-stranded RNA structures were deduced to form in test tubes almost 60 years ago. Despite this early discovery, only a handful of RNA triple helices have been validated in eukaryotic cellular RNAs. The long-term goal of the Brown laboratory is to understand the cellular, biochemical, and structural roles of RNA triple helices using the MALAT1 triple helix as a model. This triple helix forms at the 3¢ end of a cancer-promoting long noncoding RNA, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), and is required for the accumulation of MALAT1 in cells. We recently discovered that the MALAT1 triple helix interacts with METTL16 (methyltransferase-like protein 16), a putative RNA methyltransferase. The Brown laboratory is exploring several key questions. What is the cellular function of METTL16 and the METTL16-MALAT1 complex? Does METTL16 play a role in cancer? Does the METTL16-MALAT1 complex contribute to the molecular function of MALAT1 in cancer? To investigate these questions, we are using in vitro and cell-based biochemical methods. Ultimately, these mechanistic studies of the MALAT1 triple helix and METTL16 will advance our understanding of their roles in cancer.
“Methyltransferase-like protein 16 binds the 3¢-terminal triple helix of MALAT1 long noncoding RNA.” J.A. Brown, C.G. Kinzig, S.J. DeGregorio, J.A. Steitz, Proc Natl Acad Sci USA. 2016, 113(49), 14013-8.
“Structural insights into the stabilization of MALAT1 noncoding RNA by a bipartite triple helix.” J.A. Brown, D. Bulkley, J. Wang, M.L. Valenstein, T.A. Yario, T.A. Steitz, J.A. Steitz, Nat Struct Mol Biol. 2014, 21(7), 633-640.
“Formation of triple-helical structures by the 3′-end sequences of MALAT1 and MENβ noncoding RNAs.” J.A. Brown, M.L. Valenstein, T.A. Yario, K.T. Tycowski, J.A. Steitz, Proc Natl Acad Sci USA. 2012, 109(47), 19202-7.