Transcriptome changes in DM1 patients’ tissues are governed by the RNA interference pathway
Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by pathogenic expansions of CTG repeats. The expanded repeats are transcribed to long RNA and induce cellular toxicity. Recent studies suggest that the CUG repeats are processed by the RNA interference (RNAi) pathway to generate small...
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Published in | Frontiers in molecular biosciences Vol. 9; p. 955753 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
19.08.2022
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Subjects | |
Online Access | Get full text |
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Summary: | Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by pathogenic expansions of CTG repeats. The expanded repeats are transcribed to long RNA and induce cellular toxicity. Recent studies suggest that the CUG repeats are processed by the RNA interference (RNAi) pathway to generate small interfering repeated RNA (siRNA). However, the effects of the CTG repeat-derived siRNAs remain unclear. We hypothesize that the RNAi machinery in DM1 patients generates distinct gene expression patterns that determine the disease phenotype in the individual patient. The abundance of genes with complementary repeats that are targeted by siRNAs in each tissue determines the way that the tissue is affected in DM1. We integrated and analyzed published transcriptome data from muscle, heart, and brain biopsies of DM1 patients, and revealed shared, characteristic changes that correlated with disease phenotype. These signatures are overrepresented by genes and transcription factors bearing endogenous CTG/CAG repeats and are governed by aberrant activity of the RNAi machinery, miRNAs, and a specific gain-of-function of the CTG repeats. Computational analysis of the DM1 transcriptome enhances our understanding of the complex pathophysiology of the disease and may reveal a path for cure. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Peter Meinke, LMU Munich University Hospital, Germany Reviewed by: Agnieszka Fiszer, Institute of Bioorganic Chemistry (PAS), Poland This article was submitted to RNA Networks and Biology, a section of the journal Frontiers in Molecular Biosciences Edited by: Sybille Krauß, University of Siegen, Germany |
ISSN: | 2296-889X 2296-889X |
DOI: | 10.3389/fmolb.2022.955753 |