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Molecular Mechanisms of Myotonic Dystrophy: RNA-Mediated Pathogenesis and RNA-Binding Proteins

  • Yoshihiro KinoEmail author
  • Jun-ichi Satoh
  • Shoichi Ishiura
Chapter
  • 343 Downloads

Abstract

Since the identification of a repeat expansion as a causative mutation of myotonic dystrophy (dystrophia myotonica, DM) type 1 (DM1), several pathomechanisms have been proposed. Among them, an RNA-mediated mechanism is thought to play a central role in the pathogenesis of DM. In both DM1 and DM type 2 (DM2), mutated alleles produce transcripts containing an expanded CUG (DM1) or CCUG (DM2) tract. These aberrant RNAs accumulate in nuclei and form ribonuclear inclusions or nuclear RNA foci, a pathological hallmark of DM. These transcripts sequester muscleblind-like (MBNL) proteins, which regulate alternative splicing and other RNA processing. Loss of function of MBNL proteins in mouse models recapitulates many aspects of DM. In this chapter, the pathomechanisms of DM1 and DM2 are discussed, with an emphasis on the roles of RNA-binding proteins together with recent findings in this field.

Keywords

RNA foci MBNL proteins CELF proteins Alternative splicing RAN translation RNA gelation 

Notes

Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to Y.K. (16K09683) and by the Dementia Drug Resource Development Center Project (DRC), MEXT Japan (S1511016). This work was also supported in part by an Intramural Research Grant (26-8) for Neurological and Psychiatric Disorders of NCNP, a research grant for Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare (MHLW; H26-Sinkeikinn-ippan-004) and a Grant-in-Aid from the MHLW of Japan (to S.I.).

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Yoshihiro Kino
    • 1
    Email author
  • Jun-ichi Satoh
    • 1
  • Shoichi Ishiura
    • 2
  1. 1.Department of Bioinformatics and Molecular NeuropathologyMeiji Pharmaceuticals UniversityTokyoJapan
  2. 2.Faculty of Life and Medical SciencesDoshisha UniversityKyotoJapan

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