Molecules, Vol. 25, Pages 525: Structural Diversity of Sense and Antisense RNA Hexanucleotide Repeats Associated with ALS and FTLD

Molecules, Vol. 25, Pages 525: Structural Diversity of Sense and Antisense RNA Hexanucleotide Repeats Associated with ALS and FTLD Molecules doi: 10.3390/molecules25030525 Authors: Božič Zalar Rogelj Plavec Šket The hexanucleotide expansion GGGGCC located in C9orf72 gene represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Since the discovery one of the non-exclusive mechanisms of expanded hexanucleotide G4C2 repeats involved in ALS and FTLD is RNA toxicity, which involves accumulation of pathological sense and antisense RNA transcripts. Formed RNA foci sequester RNA-binding proteins, causing their mislocalization and, thus, diminishing their biological function. Therefore, structures adopted by pathological RNA transcripts could have a key role in pathogenesis of ALS and FTLD. Utilizing NMR spectroscopy and complementary methods, we examined structures adopted by both guanine-rich sense and cytosine-rich antisense RNA oligonucleotides with four hexanucleotide repeats. While both oligonucleotides tend to form dimers and hairpins, the equilibrium of these structures differs with antisense oligonucleotide being more sensitive to changes in pH and sense oligonucleotide to temperature. In the presence of K+ ions, guanine-rich sense RNA oligonucleotide also adopts secondary structures called G-quadruplexes. Here, we also observed, for the first time, that antisense RNA oligonucleotid...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research

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Source: Neuron - Category: Neuroscience Source Type: research
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A repeat expansion in the C9orf72-SMCR8 complex subunit (C9orf72) is the most common genetic cause of two debilitating neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (...
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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