位於人類第9對染色體第72開放讀框 (Chromosome 9 open reading frame 72, C9ORF72) 基因的內顯子片段中，GGGGCC六核苷酸重複序列的擴張，被認為與家族性遺傳的肌萎縮性脊髓側索硬化症 (Amyotrophic lateral sclerosis, ALS) 以及額顳葉失智症 (Frontotemporal dementia, FTD) 神經退化性疾病的發作有高度的相關性。正常人該區塊擁有的GGGGCC序列重複次數低於20至25以下，然而患者被發現該序列重複次數高達到數十至數百。根據先前研究指出，GGGGCC的重複序列能以折疊方式形成多樣二級結構，這些二級結構會導致在轉錄時該重複序列擴張，亦或大量的RNA結合蛋白與RNA片段聚集形成RNA灶 (foci)，使RNA結合蛋白功能失調，另外，轉譯時亦會因為其二級結構誘發非正常轉譯進行，進而產生二肽重複蛋白，這些二肽重複蛋白透過錯誤折疊堆積造成毒性，這兩方面因素對C9ORF72導致的ALS和FTD患者發病過程造成主要的影響。
在本篇論文中，利用單分子螢光共振能量轉移 (Single molecule fluorescence resonance energy transfer, smFRET) 光譜，研究d(GGGGCC) 重複序列的結構，觀測該序列與其自身能轉譯出的二肽重複蛋白之間的交互作用，實驗結果發現重複次數超過20以上帶正電的二肽重複蛋白 (GR)n 會與d(GGGGCC)n 產生作用並對於序列及結構擁有專一性，會針對d(GGGGCC)n 髮夾型的二級結構造成影響，結構的變化會隨時間逐漸恢復至穩定狀態，然而恢復的時間長短受 (GR)n 添加的濃度影響，由此推斷 (GR)n 可能藉由與d(GGGGCC)n 交互作用後以某種形式被消耗掉，並且 (GR)n 反應後的產物不會再與d(GGGGCC)n 的二級結構進行反應。

Hexanucleotide sequence GGGGCC repeat expansion in Chromosome 9 open reading frame 72 (C9ORF72) intron is considered to be the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) which are severe neurodegenerative diseases. The number of GGGGCC sequence repeat units in patients is believed to be at least several tens to hundreds of, compared with fewer than 20 to 25 in healthy controls. The GGGGCC repeats could fold into different secondary structures leading repeat sequence expansion or sequestration of RNA binding proteins by repeat-expanded RNA forming toxic RNA foci, during transcription. In the translation step, the secondary structures would also induce repeat-associated non-ATG (RAN) translation. This noncanonical translation would generate dipeptide repeat (DPR) proteins forming intracellular aggregates.
Here, we use single-molecule fluorescence resonance energy transfer (smFRET) spectroscopy to study the interaction between DPR proteins and d(GGGGCC)n through DNA secondary structure conformational change. The results show that the positive charge dipeptide (GR)n repeats number over 20 have interaction with d(GGGGCC)n and specificity to sequence and structure. Effect on the hairpin structure would gradually recover and back to steady state over time controlled by (GR)n concentration. It seems that (GR)n is consumed and the product would not have reaction with d(GGGGCC)n secondary structure.

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