RNA-Binding Protein Misregulation in Microsatellite Expansion Disorders

  • Marianne Goodwin
  • Maurice S. Swanson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 825)


RNA-binding proteins (RBPs) play pivotal roles in multiple cellular pathways from transcription to RNA turnover by interacting with RNA sequence and/or structural elements to form distinct RNA–protein complexes. Since these complexes are required for the normal regulation of gene expression, mutations that alter RBP functions may result in a cascade of deleterious events that lead to severe disease. Here, we focus on a group of hereditary disorders, the microsatellite expansion diseases, which alter RBP activities and result in abnormal neurological and neuromuscular phenotypes. While many of these diseases are classified as adult-onset disorders, mounting evidence indicates that disruption of normal RNA–protein interaction networks during embryogenesis modifies developmental pathways, which ultimately leads to disease manifestations later in life. Efforts to understand the molecular basis of these disorders has already uncovered novel pathogenic mechanisms, including RNA toxicity and repeat-associated non-ATG (RAN) translation, and current studies suggest that additional surprising insights into cellular regulatory pathways will emerge in the future.


Amyotrophic lateral sclerosis/frontotemporal dementia Microsatellite Myotonic dystrophy Neurological disease Oculopharyngeal muscular dystrophy RNA processing RNA toxicity Spinocerebellar ataxia 



Our studies on microsatellite expansion disease mechanisms are supported by the NIH (AR046799, NS058901), the Keck Foundation, and the Muscular Dystrophy Association. The authors thank T. Ashizawa, J. Cleary, and L. Ranum for comments on the manuscript.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Molecular Genetics and MicrobiologyUniversity of Florida, College of Medicine, Cancer Genetics Research ComplexGainesvilleUSA

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