CAG repeat RNA as an auxiliary toxic agent in polyglutamine disorders

Wojciechowska, Marzena; Krzyżosiak, Włodzimierz J.

doi:10.4161/rna.8.4.15397

Cited by 41 publications

(43 citation statements)

References 67 publications

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“…Expansion of the (CGG) n ⅐(CCG) n repeat in the FMR1 gene can lead to three distinct syndromes, fragile X mental retardation, primary ovarian insufficiency, and fragile X-associated ataxia, where the latter is thought be mediated through sequestration of RNA-binding proteins bound to a toxic CGG-containing RNA found in nuclear foci in FXTAS brains (9). Expansions of coding CAG repeats, as occur in Huntington disease and several spinocerebellar ataxias, lead to toxic polyglutamine proteins, but some polyglutamine diseases are also thought to have toxic CAG RNAs (10). An underlying feature of all repeat diseases is the expansion of an (often bidirectionally) transcribed repeat tract that has the potential to form unusual DNA and RNA structures (6,8,11).…”

mentioning

confidence: 99%

The Disease-associated r(GGGGCC) Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

Reddy

Zamiri

Stanley

et al. 2013

Journal of Biological Chemistry

291

314

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mentioning

confidence: 99%

The Disease-associated r(GGGGCC) Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

Reddy

Zamiri

Stanley

et al. 2013

Journal of Biological Chemistry

291

314

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“…Similarly, a Drosophila model of spinocerebellar ataxia 3 expressing a non-coding expanded CAG repeat elicited neurodegeneration (Li et al, 2008). Interestingly, up-regulating the fly MBNL homolog caused a marked increase in polyglutamine-containing ataxin3 neurodegeneration, which is the opposite direction of interaction to that seen with the CUG repeat expression (Houseley et al, 2005; Li et al, 2008; Braida et al, 2010; Wojciechowska and Krzyzosiak, 2011). This effect was also investigated in a mouse model which expressed CAG repeats in the 3′ UTR of a green fluorescence protein reporter (Hsu et al, 2011).…”

Section: Rna Dominant Neurological Disordersmentioning

confidence: 95%

Neurodegeneration the RNA way

Renoux

Todd

2012

Progress in Neurobiology

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The expression, processing, transport and activities of both coding and non-coding RNAs play critical roles in normal neuronal function and differentiation. Over the past decade, these same pathways have come under scrutiny as potential contributors to neurodegenerative disease. Here we focus broadly on the roles of RNA and RNA processing in neurodegeneration. We first discuss a set of “RNAopathies”, where non-coding repeat expansions drive pathogenesis through a surprisingly diverse set of mechanisms. We next explore an emerging class of “RNA binding proteinopathies” where redistribution and aggregation of the RNA binding proteins TDP-43 or FUS contribute to a potentially broad range of neurodegenerative disorders. Lastly, we delve into the potential contributions of alterations in both short and long non-coding RNAs to neurodegenerative illness.

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“…Bidirectional transcription across expanded microsatellites has been observed in several disorders. This presents additional challenges for elucidating disease mechanisms, since a single expanded repeat DNA sequence has the potential to encode multiple toxic units: sense transcripts and protein translated from those transcripts, as well as antisense transcripts and their translated proteins [recently reviewed in (Batra et al, 2010; Krzyzosiak et al, 2011; Wojciechowska and Krzyzosiak, 2011b)]. Many groups have worked to carefully identify the pathogenic contribution of each of these entities to neurological disease.…”

Section: Dna Microsatellites Encode Multiple Toxic Unitsmentioning

confidence: 99%

RNA-binding proteins in microsatellite expansion disorders: Mediators of RNA toxicity

Echeverria

Cooper

2012

Brain Research

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Although protein-mediated toxicity in neurological disease has been extensively characterized, RNA-mediated toxicity is an emerging mechanism of pathogenesis. In microsatellite expansion disorders, expansion of repeated sequences in noncoding regions gives rise to RNA that produces a toxic gain of function, while expansions in coding regions can disrupt protein function as well a produce toxic RNA. The toxic RNA typically aggregates into nuclear foci and contributes to disease pathogenesis. In many cases, toxicity of the RNA is caused by the disrupted functions of RNA-binding proteins. We will discuss evidence for RNA-mediated toxicity in microsatellite expansion disorders. Different microsatellite expansion disorders are linked with alterations in the same as well as disease-specific RNA binding proteins. Recent studies have shown that microsatellite expansions can encode multiple repeat-containing toxic RNAs through bidirectional transcription and protein species through repeat-associated non-ATG translation. We will discuss approaches that have characterized the toxic contributions of these various factors.

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CAG repeat RNA as an auxiliary toxic agent in polyglutamine disorders

Cited by 41 publications

References 67 publications

The Disease-associated r(GGGGCC) Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

The Disease-associated r(GGGGCC) Repeat from the C9orf72 Gene Forms Tract Length-dependent Uni- and Multimolecular RNA G-quadruplex Structures

Neurodegeneration the RNA way

RNA-binding proteins in microsatellite expansion disorders: Mediators of RNA toxicity

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