書誌事項
- タイトル別名
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- GCG repeat expansion in <i>ARX</i> gene inhibits ARX protein translation through the ectopic formation of RNA G-quadruplex
抄録
<p>Aristaless-related homeobox (ARX) is a crucial gene involved in the development of interneurons in the fetal brain. The ARX gene mutations are a significant contributor to X-Linked intellectual disability (XLID) including epilepsy. We investigated that the pathological mechanism of ARX-associated XLID in the most frequent polyalanine expansion mutation [c.334ins(GCG)7], termed GCG17. Biophysical analyses in circular dichroism (CD) spectra and thioflavin T assay revealed that GCG17 formed a parallel RNA G-quadruplex (G4RNA) exhibiting the stereotypical potassium specificity in vitro, but a control GCG10 and GCG10+GCA7 repeat RNA did not. Consistent with the results, the GCG17 stably expressing cells decreased the polyalanine expression compared to that of GCG10 and GCG10+GCA7 cells without changing these mRNA levels. G4RNAs are secondary structures proposed to function as negative regulators of post-transcriptional mRNA translation. Further, a mouse model of ARX-associated XLID shows the decrease of ARX protein translation. Taken together, inhibition of ARX protein translation by GCG17-derived ectopic G4RNA formation may cause ARX-associated XLID.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 94 (0), 2-O-B1-2-, 2021
公益社団法人 日本薬理学会
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キーワード
詳細情報 詳細情報について
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- CRID
- 1390005966211638144
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- NII論文ID
- 130008001444
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可