E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Myotonic Dystrophy: From Molecular Pathogenesis to Therapeutics"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 15 August 2019.

Special Issue Editor

Guest Editor
Prof. Lubov Timchenko

Department of Pediatrics, Division of Neurology, Cincinnati Children’s Hospital, Medical Center, 3333 Burnet Ave, Cincinnati, Ohio, US
E-Mail
Interests: genetic diseases with unstable expansions; RNA-binding proteins; molecular biology and biochemistry

Special Issue Information

Dear Colleagues,

Myotonic dystrophies (DM) type 1 and type 2 are complex genetic diseases affecting many tissues, including the skeletal muscle, heart and brain. DM1 and DM2 are caused by unstable expansions of CTG (DM1) and CCTG (DM2) repeats. Both diseases do not have a cure. The molecular studies of DM identified the major mechanisms for these disorders, associated with the toxic effects of the mutant RNAs, containing long CUG and CCUG repeats. However, the mutant RNAs in DM1 and DM2 might affect additional intracellular pathways, increasing the complexity of molecular pathogenesis. This Special Issue will summarize findings describing the molecular mechanisms of DM1 and DM2 and will discuss how these advances can be used for the development of the clinical studies in DM1 and DM2.  

Prof. Lubov Timchenko
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (1 paper)

View options order results:
result details:
Displaying articles 1-1
Export citation of selected articles as:

Review

Open AccessReview
Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myotonic Dystrophy
Int. J. Mol. Sci. 2019, 20(13), 3365; https://doi.org/10.3390/ijms20133365
Received: 7 June 2019 / Revised: 27 June 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
PDF Full-text (3168 KB) | HTML Full-text | XML Full-text
Abstract
Short tandem repeat (STR) or microsatellite, expansions underlie more than 50 hereditary neurological, neuromuscular and other diseases, including myotonic dystrophy types 1 (DM1) and 2 (DM2). Current disease models for DM1 and DM2 propose a common pathomechanism, whereby the transcription of mutant DMPK [...] Read more.
Short tandem repeat (STR) or microsatellite, expansions underlie more than 50 hereditary neurological, neuromuscular and other diseases, including myotonic dystrophy types 1 (DM1) and 2 (DM2). Current disease models for DM1 and DM2 propose a common pathomechanism, whereby the transcription of mutant DMPK (DM1) and CNBP (DM2) genes results in the synthesis of CUG and CCUG repeat expansion (CUGexp, CCUGexp) RNAs, respectively. These CUGexp and CCUGexp RNAs are toxic since they promote the assembly of ribonucleoprotein (RNP) complexes or RNA foci, leading to sequestration of Muscleblind-like (MBNL) proteins in the nucleus and global dysregulation of the processing, localization and stability of MBNL target RNAs. STR expansion RNAs also form phase-separated gel-like droplets both in vitro and in transiently transfected cells, implicating RNA-RNA multivalent interactions as drivers of RNA foci formation. Importantly, the nucleation and growth of these nuclear foci and transcript misprocessing are reversible processes and thus amenable to therapeutic intervention. In this review, we provide an overview of potential DM1 and DM2 pathomechanisms, followed by a discussion of MBNL functions in RNA processing and how multivalent interactions between expanded STR RNAs and RNA-binding proteins (RBPs) promote RNA foci assembly. Full article
(This article belongs to the Special Issue Myotonic Dystrophy: From Molecular Pathogenesis to Therapeutics)
Figures

Figure 1

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top