Long ncRNA expression abnormality in polyglutmine diseases

• Project/Area Number: 25253066
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Doshisha University (2014-2015); Juntendo University (2013)
• Principal Investigator: Nukina Nobuyuki 同志社大学, 脳科学研究科, 教授 (10134595)
• Co-Investigator(Kenkyū-buntansha): Miyazaki Haruko 独立行政法人理化学研究所, 視床発生研究チーム, 研究員 (80525890) ; 下郡 智美 独立行政法人理化学研究所, 視床発生研究チーム, チームリーダー (30391981)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000); Fiscal Year 2015: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000); Fiscal Year 2014: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2013: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
• Keywords: ポリグルタミン病 / 遺伝子発現 / lncRNA / 非コードRNA / 中型有棘神経細胞 / lincRNA

Outline of Final Research Achievements

To reveal the pathological significance of the gene expression abnormality in Huntington disease(HD), we developed the method to identify the gene expression changes in specific neuronal fraction such as medium spiny neurons(MSN) in striatum. We isolated MSN using cell sorter from control and HD model mice with Venus expression in MSN, then compared their gene expressions with microarray. We identified many genes, which showed expression changes, those include previously reported and unreported ones.Those could be confirmed by RT-PCR if the expression levels are above the certain level. We also identified the expression abnormality of long non-coding RNA, however, many of them showed low expression level. Thus, new methods for confirmation is necessary.

Research Products

• [Journal Article] Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy. (2016)
  • Author(s): Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, Kino Y,.......Zimmer T, Furling D, Takahashi MP, Charlet-Berguerand N.
  • Journal Title: Nat Commun. Volume: 7 Issue: 1 Pages: 11067-11067
  • DOI: 10.1038/ncomms11067
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genome-wide analyses in neuronal cells reveal that upstream transcription factors regulate lysosomal gene expression. (2016)
  • Author(s): Yamanaka T, Tosaki A, Kurosawa M, Shimogori T, Hattori N, Nukina N
  • Journal Title: FEBS J Volume: 283(6) Issue: 6 Pages: 1077-87
  • DOI: 10.1111/febs.13650
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] erine 403-phosphorylated p62/SQSTM1 immunoreactivity in inclusions of neurodegenerative diseases (2015)
  • Author(s): Kurosawa,M., Matsumoto,G., Sumikura,H., Hatsuta,H., Murayama,S., Sakurai,T., Shimogori,T., Hattori,N. and Nukina,N.
  • Journal Title: Neurosci. Res. Volume: 103 Pages: 64-70
  • DOI: 10.1016/j.neures.2015.08.002
  • Peer Reviewed / Open Access
• [Journal Article] TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation. (2015)
  • Author(s): Matsumoto G, Shimogori T, Hattori N, Nukina N.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 15 Pages: 4429-42
  • DOI: 10.1093/hmg/ddv179
  • Peer Reviewed
• [Journal Article] FUS/TLS deficiency causes behavioral and pathological abnormalities distinct from amyotrophic lateral sclerosis. (2015)
  • Author(s): Kino Y, Washizu C, Kurosawa M, Yamada M, Miyazaki H, Akagi T, Hashikawa T, Doi H, Takumi T, Hicks GG, Hattori N, Shimogori T, Nukina N.
  • Journal Title: Acta Neuropathol Commun Volume: 3 Issue: 1 Pages: 24-24
  • DOI: 10.1186/s40478-015-0202-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization (2014)
  • Author(s): Yamanaka, T., Tosaki, A., Kurosawa, M., Matsumoto, G., Koike, M., Uchiyama, Y., Maity, S.N., Shimogori, T., Hattori, N. & Nukina, N.
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 3354-3354
  • DOI: 10.1038/ncomms4354
  • Peer Reviewed
• [Journal Article] Functional diversity of protein fibrillar aggregates from physiology to RNA granules to neurodegenerative diseases (2013)
  • Author(s): Furukawa, Y. & Nukina, N.
  • Journal Title: Biochim. Biophys. Acta Volume: 1832 Issue: 8 Pages: 1271-1278
  • DOI: 10.1016/j.bbadis.2013.04.011
  • Peer Reviewed
• [Presentation] Cell type-specific neruopathologies in NF-Y mutant mice. (2015)
  • Author(s): 山中智行、戸崎麻子、宮崎晴子、黒澤大、小池正人、内山安男、Sankar N. Maity、三澤日出巳、服部信孝、貫名信行
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸（神戸国際会議場）
  • Year and Date: 2015-07-28
• [Remarks] 同志社大学大学院脳科学研究科認知記憶加齢部門
  • URL: http://brainscience.doshisha.ac.jp/introduction/pat/ca.html
• [Remarks] 同志社大学大大学院脳科学研究科貫名研究室
  • URL: http://snp.hippy.jp/