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Open AccessArticle

Secondary Structural Model of Human MALAT1 Reveals Multiple Structure–Function Relationships

1
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
2
Department of Chemistry and Biochemistry, Biomolecular Science and Engineering Program, University of California at Santa Barbara, Santa Barbara, CA 93106, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(22), 5610; https://doi.org/10.3390/ijms20225610 (registering DOI)
Received: 24 October 2019 / Accepted: 7 November 2019 / Published: 9 November 2019
(This article belongs to the Special Issue Non-Coding RNA Biogenesis and Function)
Human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an abundant nuclear-localized long noncoding RNA (lncRNA) that has significant roles in cancer. While the interacting partners and evolutionary sequence conservation of MALAT1 have been examined, much of the structure of MALAT1 is unknown. Here, we propose a hypothetical secondary structural model for 8425 nucleotides of human MALAT1 using three experimental datasets that probed RNA structures in vitro and in various human cell lines. Our model indicates that approximately half of human MALAT1 is structured, forming 194 helices, 13 pseudoknots, five structured tetraloops, nine structured internal loops, and 13 intramolecular long-range interactions that give rise to several multiway junctions. Evolutionary conservation and covariation analyses support 153 of 194 helices in 51 mammalian MALAT1 homologs and 42 of 194 helices in 53 vertebrate MALAT1 homologs, thereby identifying an evolutionarily conserved core that likely has important functional roles in mammals and vertebrates. Data mining revealed that RNA modifications, somatic cancer-associated mutations, and single-nucleotide polymorphisms may induce structural rearrangements that sequester or expose binding sites for several cancer-associated microRNAs. Our findings reveal new mechanistic leads into the roles of MALAT1 by identifying several intriguing structure–function relationships in which the dynamic structure of MALAT1 underlies its biological functions. View Full-Text
Keywords: long noncoding RNA; secondary structure; MALAT1; m6A; cancer long noncoding RNA; secondary structure; MALAT1; m6A; cancer
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McCown, P.J.; Wang, M.C.; Jaeger, L.; Brown, J.A. Secondary Structural Model of Human MALAT1 Reveals Multiple Structure–Function Relationships. Int. J. Mol. Sci. 2019, 20, 5610.

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