Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase
Unstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected indi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/826 |
| _version_ | 1797612873579495424 |
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| author | Ana S. Figueiredo Joana R. Loureiro Sandra Macedo-Ribeiro Isabel Silveira |
| author_facet | Ana S. Figueiredo Joana R. Loureiro Sandra Macedo-Ribeiro Isabel Silveira |
| author_sort | Ana S. Figueiredo |
| collection | DOAJ |
| description | Unstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected individuals. Recent evidence indicates that alterations of the dynamic or material properties of biomolecular condensates assembled by liquid/liquid phase separation are critical for the formation of these aggregates. This is a thermodynamically-driven and reversible local phenomenon that condenses macromolecules into liquid-like compartments responsible for compartmentalizing molecules required for vital cellular processes. Disease-associated repeat expansions modulate the phase separation properties of RNAs and proteins, interfering with the composition and/or the material properties of biomolecular condensates and resulting in the formation of abnormal aggregates. Since several repeat expansions have arisen in genes encoding crucial players in transcription, this raises the hypothesis that wide gene expression dysregulation is common to multiple repeat expansion diseases. This review will cover the impact of these mutations in the formation of aberrant aggregates and how they modify gene transcription. |
| first_indexed | 2024-03-11T06:47:58Z |
| format | Article |
| id | doaj.art-c388c7432f5f43d08e0688b5f5606c34 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:47:58Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c388c7432f5f43d08e0688b5f5606c342023-11-17T10:12:23ZengMDPI AGCells2073-44092023-03-0112682610.3390/cells12060826Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in PhaseAna S. Figueiredo0Joana R. Loureiro1Sandra Macedo-Ribeiro2Isabel Silveira3Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, PortugalUnstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected individuals. Recent evidence indicates that alterations of the dynamic or material properties of biomolecular condensates assembled by liquid/liquid phase separation are critical for the formation of these aggregates. This is a thermodynamically-driven and reversible local phenomenon that condenses macromolecules into liquid-like compartments responsible for compartmentalizing molecules required for vital cellular processes. Disease-associated repeat expansions modulate the phase separation properties of RNAs and proteins, interfering with the composition and/or the material properties of biomolecular condensates and resulting in the formation of abnormal aggregates. Since several repeat expansions have arisen in genes encoding crucial players in transcription, this raises the hypothesis that wide gene expression dysregulation is common to multiple repeat expansion diseases. This review will cover the impact of these mutations in the formation of aberrant aggregates and how they modify gene transcription.https://www.mdpi.com/2073-4409/12/6/826liquid/liquid phase separationRNA-binding proteinRNA/protein aggregatespolyalaninepolyglutamineNIID |
| spellingShingle | Ana S. Figueiredo Joana R. Loureiro Sandra Macedo-Ribeiro Isabel Silveira Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase Cells liquid/liquid phase separation RNA-binding protein RNA/protein aggregates polyalanine polyglutamine NIID |
| title | Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase |
| title_full | Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase |
| title_fullStr | Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase |
| title_full_unstemmed | Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase |
| title_short | Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase |
| title_sort | advances in nucleotide repeat expansion diseases transcription gets in phase |
| topic | liquid/liquid phase separation RNA-binding protein RNA/protein aggregates polyalanine polyglutamine NIID |
| url | https://www.mdpi.com/2073-4409/12/6/826 |
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