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Evaluation of the Interplay between the ADAR Editome and Immunotherapy in Melanoma
Hypothesis

Secondary Structural Model of MALAT1 Becomes Unstructured in Chronic Myeloid Leukemia and Undergoes Structural Rearrangement in Cervical Cancer

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
*
Author to whom correspondence should be addressed.
Present address: Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA.
Received: 30 November 2020 / Revised: 11 January 2021 / Accepted: 11 January 2021 / Published: 13 January 2021
(This article belongs to the Special Issue Systematic Analysis of lncRNA Structures and Functions)
Long noncoding RNAs (lncRNAs) influence cellular function through binding events that often depend on the lncRNA secondary structure. One such lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is upregulated in many cancer types and has a myriad of protein- and miRNA-binding sites. Recently, a secondary structural model of MALAT1 in noncancerous cells was proposed to form 194 hairpins and 13 pseudoknots. That study postulated that, in cancer cells, the MALAT1 structure likely varies, thereby influencing cancer progression. This work analyzes how that structural model is expected to change in K562 cells, which originated from a patient with chronic myeloid leukemia (CML), and in HeLa cells, which originated from a patient with cervical cancer. Dimethyl sulfate-sequencing (DMS-Seq) data from K562 cells and psoralen analysis of RNA interactions and structure (PARIS) data from HeLa cells were compared to the working structural model of MALAT1 in noncancerous cells to identify sites that likely undergo structural alterations. MALAT1 in K562 cells is predicted to become more unstructured, with almost 60% of examined hairpins in noncancerous cells losing at least half of their base pairings. Conversely, MALAT1 in HeLa cells is predicted to largely maintain its structure, undergoing 18 novel structural rearrangements. Moreover, 50 validated miRNA-binding sites are affected by putative secondary structural changes in both cancer types, such as miR-217 in K562 cells and miR-20a in HeLa cells. Structural changes unique to K562 cells and HeLa cells provide new mechanistic leads into how the structure of MALAT1 may mediate cancer in a cell-type specific manner. View Full-Text
Keywords: cancer; RNA secondary structure; DMS-Seq; PARIS; miRNAs cancer; RNA secondary structure; DMS-Seq; PARIS; miRNAs
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MDPI and ACS Style

Wang, M.C.; McCown, P.J.; Schiefelbein, G.E.; Brown, J.A. Secondary Structural Model of MALAT1 Becomes Unstructured in Chronic Myeloid Leukemia and Undergoes Structural Rearrangement in Cervical Cancer. Non-Coding RNA 2021, 7, 6. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010006

AMA Style

Wang MC, McCown PJ, Schiefelbein GE, Brown JA. Secondary Structural Model of MALAT1 Becomes Unstructured in Chronic Myeloid Leukemia and Undergoes Structural Rearrangement in Cervical Cancer. Non-Coding RNA. 2021; 7(1):6. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010006

Chicago/Turabian Style

Wang, Matthew C., Phillip J. McCown, Grace E. Schiefelbein, and Jessica A. Brown 2021. "Secondary Structural Model of MALAT1 Becomes Unstructured in Chronic Myeloid Leukemia and Undergoes Structural Rearrangement in Cervical Cancer" Non-Coding RNA 7, no. 1: 6. https://0-doi-org.brum.beds.ac.uk/10.3390/ncrna7010006

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