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由8-溴鸟苷修饰的CGG三核苷酸重复序列组成的RNA双链体二聚体的结构表征：一种新型的RNA四链体结构

Structural characterization of a dimer of RNA duplexes composed of 8-bromoguanosine modified CGG trinucleotide repeats: a novel architecture of RNA quadruplexes.

作者信息

Gudanis Dorota, Popenda Lukasz, Szpotkowski Kamil, Kierzek Ryszard, Gdaniec Zofia

机构信息

Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Noskowskiego 12/14, Poland.

NanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznan, Umultowska 85, Poland.

出版信息

Nucleic Acids Res. 2016 Mar 18;44(5):2409-16. doi: 10.1093/nar/gkv1534. Epub 2016 Jan 6.

DOI:10.1093/nar/gkv1534
PMID:26743003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4797283/
Abstract

Fragile X syndrome and fragile X-associated tremor/ataxia syndrome (FXTAS) are neurodegenerative disorders caused by the pathogenic expansion of CGG triplet repeats in the FMR1 gene. FXTAS is likely to be caused by a 'toxic' gain-of-function of the FMR1 mRNA. We provide evidence for the existence of a novel quadruplex architecture comprising CGG repeats. The 8-bromoguanosine ((Br)G)-modified molecule GC(Br)GGCGGC forms a duplex in solution and self-associates via the major groove to form a four-stranded, antiparallel (GC(Br)GGCGGC)4 RNA quadruplex with (Br)G3:G6:(Br)G3:G6 tetrads sandwiched between mixed G:C:G:C tetrads. Self-association of Watson-Crick duplexes to form a four-stranded structure has previously been predicted; however, no experimental evidence was provided. This novel four-stranded RNA structure was characterized using a variety of experimental methods, such as native gel electrophoresis, NMR spectroscopy, small-angle X-ray scattering and electrospray ionization mass spectrometry.

摘要

脆性X综合征和脆性X相关震颤/共济失调综合征（FXTAS）是由FMR1基因中CGG三联体重复序列的致病性扩增引起的神经退行性疾病。FXTAS可能是由FMR1 mRNA的“毒性”功能获得所致。我们提供了一种包含CGG重复序列的新型四链体结构存在的证据。8-溴鸟苷（（Br）G）修饰的分子GC（Br）GGCGGC在溶液中形成双链，并通过大沟自缔合形成四链反平行（GC（Br）GGCGGC）4 RNA四链体，其中（Br）G3:G6:（Br）G3:G6四重体夹在混合的G:C:G:C四重体之间。此前曾预测沃森-克里克双链体会自缔合形成四链结构；然而，未提供实验证据。这种新型四链RNA结构通过多种实验方法进行了表征，如非变性凝胶电泳、核磁共振光谱、小角X射线散射和电喷雾电离质谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/ce4c3e3f75fc/gkv1534fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/eab8ac62246f/gkv1534fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/bd2ed3f415fd/gkv1534fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/801c8a078868/gkv1534fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/2b1dcb51a515/gkv1534fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/85596a1be29f/gkv1534fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/ce4c3e3f75fc/gkv1534fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/eab8ac62246f/gkv1534fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/bd2ed3f415fd/gkv1534fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/801c8a078868/gkv1534fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/2b1dcb51a515/gkv1534fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/85596a1be29f/gkv1534fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e148/4797283/ce4c3e3f75fc/gkv1534fig6.jpg

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