Related Experiment Video
Updated: Apr 26, 2026
Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
Published on: September 13, 2024
Mechanisms of transcriptional dysregulation in repeat expansion disorders
Matthias Groh1, Lara Marques Silva1, Natalia Gromak1
1*Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K.
Abstract:
Approximately 40 human diseases are associated with expansion of repeat sequences. These expansions can reside within coding or non-coding parts of the genes, affecting the host gene function. The presence of such expansions results in the production of toxic RNA and/or protein or causes transcriptional repression and silencing of the host gene. Although the molecular mechanisms of expansion diseases are not well understood, mounting evidence suggests that transcription through expanded repeats plays an essential role in disease pathology. The presence of an expansion can affect RNA polymerase transcription, leading to dysregulation of transcription-associated processes, such as RNA splicing, formation of RNA/DNA hybrids (R-loops), production of antisense, short non-coding and bidirectional RNA transcripts. In the present review, we summarize current advances in this field and discuss possible roles of transcriptional defects in disease pathology.
Insights
Repeat expansion diseases involve genetic mutations affecting gene function. Transcription through these expanded repeats is crucial in disease development, impacting gene expression and cellular processes.
Area of Science:
- Genetics
- Molecular Biology
- Genomic Instability
Background:
- Approximately 40 human diseases are linked to the expansion of repetitive DNA sequences.
- These expansions can occur in coding or non-coding regions, disrupting normal gene function.
- The resulting toxic RNA/protein production or transcriptional repression contributes to disease pathology.
Purpose of the Study:
- To review current understanding of repeat expansion diseases.
- To explore the role of transcription through expanded repeats in disease mechanisms.
- To discuss the impact of transcriptional defects on disease pathology.
Main Methods:
- Literature review of current research on repeat expansion diseases.
- Analysis of molecular mechanisms involving transcription through expanded repeats.
- Discussion of evidence linking transcriptional dysregulation to disease.
Main Results:
- Transcription through expanded repeats is implicated in disease pathology.
- Expanded repeats can interfere with RNA polymerase activity and transcription-associated processes.
- Dysregulation includes altered RNA splicing, R-loop formation, and non-coding RNA production.
Conclusions:
- Transcriptional defects play a significant role in the pathology of repeat expansion diseases.
- Understanding these mechanisms is key to developing therapeutic strategies.
- Further research is needed to fully elucidate the molecular underpinnings of these disorders.
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation
01:46Epigenetic Regulation
02:35Transcription Elongation Factors
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
02:36RNA Polymerase II Accessory Proteins
02:05Duplication of Chromatin Structure
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...