第八型脊髓小腦運動失調症與ATXN8OS CUG重複擴增RNA及ATXN8多麩醯胺擴增的 蛋白相關。雖然在CTG方向被轉錄、選擇性裁接及加上polyA尾，WTXNSOS RNA上僅存在 小的開放解讀架構。為探究4TXNSOS RNA上一包含102胺基酸之ORF1及一包含41胺基酸與 多白胺酸之ORF2是否被轉譯，我們選殖了人的WTXNSOS cDNA 5’片段，置入水母及螢火蟲 雙冷光酶基因間。短暫轉染人類胚胎腎細胞及冷光報告測驗顯示，ATXN8OSRNA上帶有兩 個不依賴Cap的内部核醣體進入位置。進一步表現在同一解讀架構上的ORF1-EGFP基因亦證 實ORF1的轉譯。結合GFP抗體的西方轉潰分析顯示，上游的non-AUG密碼可能作為 ORF1-EGFP蛋白的轉譯起始密碼。ATXNSOS ORF1的生理意義及其在SCA8致病機轉的角色 仍有待釐清。

Spinocerebellar ataxia type 8 (SCA8) involves bidirectional expression of CUG (ATXN8OS) and CAG (ATXN8) expansion transcripts. Although being transcribed, alternatively spliced and polyadenylated in the CTG orientation, only small open reading frames (ORFs) were noted in ATXN8OS RNA. To investigate if a 102 amino acids containing-ORF (ORF1) and a 41 amino acids plus a polyleucine tract containing-ORF (ORF2) in the ATXN8OS RNA could be translated, we cloned 5’ region of the human ATXN8OS cDNA into dicistronic Renilla and firefly luciferase reporter. Transient transfection in human embryonic kidney (HEK)-293 cells and reporter assay revealed the presence of bipartite cap independent internal ribosome entry segments (IRESs) in the ATXN8OS RNA. The translation of ORF1 was further demonstrated by expression of chimeric construct with an in-frame ORF1-EGFP gene. Western blot with GFP antibody suggested that the expressed ORF1-EGFP protein may be initiated from an upstream non-AUG initiator. The biological meaning of the ATXN8OS ORF1 protein and its role in the pathogenesis of SCA8 remains to be determined.