A search for abnormal RNA metabolism in spinocerebellar ataxia type 31

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ISHIKAWA Kinya 東京医科歯科大学, 医学部附属病院, 教授 (30313240)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 遺伝子 / 脳 / 神経疾患 / ＲＮＡ

Outline of Final Research Achievements

We studied on human brain samples affected with spinocerebellar ataxia type 31 (SCA31). By expression analysis using microarray and RNA-seq, we found groups of genes which have meaningful alterations in their expression levels. Among those, we confirmed several genes that are down-regulated in SCA31 samples. Some of them were known to be involved in intracellular calcium homeostasis. We also found that SCA31 human Purkinje cells possess abnormal RNA structures called RNA foci which contain (UGGAA)n repeat, the transcript of (TGGAA)n repeat exclusively found in the SCA31 patients’ mutation locus. Such RNA foci were also found in cultured cells expressing SCA31 mutation constructs. These results suggest that the UGGAA repeat is involved in SCA31 pathogenesis.

Free Research Field

神経内科学