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Repeat-associated RNA structure and aberrant splicing.

Abstract

Over 30 hereditary disorders attributed to the expansion of microsatellite repeats have been identified. Despite variant nucleotide content, number of consecutive repeats, and different locations in the genome, many of these diseases have pathogenic RNA gain-of-function mechanisms. The repeat-containing RNAs can form structures in vitro predicted to contribute to the disease through assembly of intracellular RNA aggregates termed foci. The expanded repeat RNAs within these foci sequester RNA binding proteins (RBPs) with important roles in the regulation of RNA metabolism, most notably alternative splicing (AS). These deleterious interactions lead to downstream alterations in transcriptome-wide AS directly linked with disease symptoms. This review summarizes existing knowledge about the association between the repeat RNA structures and RBPs as well as the resulting aberrant AS patterns, specifically in the context of myotonic dystrophy. The connection between toxic, structured RNAs and dysregulation of AS in other repeat expansion diseases is also discussed. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.

Authors+Show Affiliations

Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.Department of Neurology, Virginia Commonwealth University, Richmond, VA 23298, USA.The RNA Institute, Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA. Electronic address: aberglund@albany.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31323433

Citation

Hale, Melissa A., et al. "Repeat-associated RNA Structure and Aberrant Splicing." Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, 2019.
Hale MA, Johnson NE, Berglund JA. Repeat-associated RNA structure and aberrant splicing. Biochim Biophys Acta Gene Regul Mech. 2019.
Hale, M. A., Johnson, N. E., & Berglund, J. A. (2019). Repeat-associated RNA structure and aberrant splicing. Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, doi:10.1016/j.bbagrm.2019.07.006.
Hale MA, Johnson NE, Berglund JA. Repeat-associated RNA Structure and Aberrant Splicing. Biochim Biophys Acta Gene Regul Mech. 2019 Jul 16; PubMed PMID: 31323433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repeat-associated RNA structure and aberrant splicing. AU - Hale,Melissa A, AU - Johnson,Nicholas E, AU - Berglund,J Andrew, Y1 - 2019/07/16/ PY - 2019/04/04/received PY - 2019/07/11/revised PY - 2019/07/12/accepted PY - 2019/7/20/pubmed PY - 2019/7/20/medline PY - 2019/7/20/entrez KW - Alternative splicing KW - Muscleblind-like (MBNL) KW - Myotonic dystrophy KW - RNA binding proteins KW - RNA structure KW - Repeat expansion diseases JF - Biochimica et biophysica acta. Gene regulatory mechanisms JO - Biochim Biophys Acta Gene Regul Mech N2 - Over 30 hereditary disorders attributed to the expansion of microsatellite repeats have been identified. Despite variant nucleotide content, number of consecutive repeats, and different locations in the genome, many of these diseases have pathogenic RNA gain-of-function mechanisms. The repeat-containing RNAs can form structures in vitro predicted to contribute to the disease through assembly of intracellular RNA aggregates termed foci. The expanded repeat RNAs within these foci sequester RNA binding proteins (RBPs) with important roles in the regulation of RNA metabolism, most notably alternative splicing (AS). These deleterious interactions lead to downstream alterations in transcriptome-wide AS directly linked with disease symptoms. This review summarizes existing knowledge about the association between the repeat RNA structures and RBPs as well as the resulting aberrant AS patterns, specifically in the context of myotonic dystrophy. The connection between toxic, structured RNAs and dysregulation of AS in other repeat expansion diseases is also discussed. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm. SN - 1876-4320 UR - https://www.unboundmedicine.com/medline/citation/31323433/Repeat-associated_RNA_structure_and_aberrant_splicing L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-9399(19)30078-1 DB - PRIME DP - Unbound Medicine ER -