Analysis of nuclear non-coding RNA upon bacterial infection

• Project/Area Number: 15K07923
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba University
• Principal Investigator: Imamura Katsutoshi 千葉大学, 大学院薬学研究院, 日本学術振興会特別研究員(PD) (60741923)
• Co-Investigator(Kenkyū-buntansha): 秋光 信佳 東京大学, アイソトープ総合センター, 教授 (40294962)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 核内RNA分解 / サルモネラ感染 / 長鎖非コードRNA / 細菌感染

Outline of Final Research Achievements

Cytoplasmic mRNA degradation controls gene expression to help eliminate pathogens during infection. However, it has remained unclear whether such regulation also extends to nuclear RNA decay. Here, we show that 145 unstable nuclear RNAs, including enhancer RNAs (eRNAs) and long noncoding RNAs (lncRNAs) are stabilized upon Salmonella infection in HeLa cells. In uninfected cells, the RNA exosome, aided by the Nuclear EXosome Targeting (NEXT) complex, degrades these labile transcripts. Upon infection, the levels of the exosome/NEXT components RRP6 and MTR4 dramatically decrease, resulting in transcript stabilization. Depletion of lncRNAs in HeLa cells triggers increased susceptibility to Salmonella infection concomitant with the deregulated expression of a distinct class of immunity-related genes, indicating that the accumulation of unstable nuclear RNAs contributes to antibacterial defense.

Research Products

• [Journal Article] 5'-Bromouridine IP Chase (BRIC)-Seq to Determine RNA Half-Lives. (2018)
  • Author(s): Yamada T, Imamachi N, Onoguchi-Mizutani R, Imamura K, Suzuki Y, Akimitsu N.
  • Journal Title: Methods Mol Biol. Volume: 1720 Pages: 1-13
  • DOI: 10.1007/978-1-4939-7540-2_1
  • ISBN: 9781493975396, 9781493975402
  • Peer Reviewed / Open Access
• [Journal Article] Diminished nuclear RNA decay upon Salmonella infection upregulates antibacterial noncoding RNAs (2018)
  • Author(s): Katsutoshi Imamura, Akiko Takaya, Yo-ichi Ishida, Yayoi Fukuoka, Toshiki Taya, Ryo Nakaki, Miho Kakeda, Naoto Imamachi, Aiko Sato, Toshimichi Yamada, Rena Onoguchi-Mizutani, Gen Akizuki, Tanzina Tanu, Kazuyuki Tao, Sotaro Miyao, Yutaka Suzuki, Masami Nagahama, Tomoko Yamamoto, Torben Heick Jensen, Nobuyoshi Akimitsu
  • Journal Title: EMBO Journal Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Characterization of the chemical structure and innate immune-stimulating activity of an extracellular polysaccharide from <i>Rhizobium</i> sp. strain M2 screened using a silkworm muscle contraction assay (2017)
  • Author(s): Urai Makoto、Aizawa Tomoko、Imamura Katsutoshi、Hamamoto Hiroshi、Sekimizu Kazuhisa
  • Journal Title: Drug Discoveries & Therapeutics Volume: 11 Issue: 5 Pages: 238-245
  • DOI: 10.5582/ddt.2017.01045
  • NAID: 130006210838
  • ISSN: 1881-7831, 1881-784X
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of RNA decay factor mediated RNA stability contributions on RNA abundance (2015)
  • Author(s): Sho Maekawa, Naoto Imamachi, Takuma Irie, Hidenori Tani, Kyoko Matsumoto, Rena Mizutani, Katsutoshi Imamura, Miho Kakeda, Tetsushi Yada, Sumio Sugano, Yutaka Suzuki and Nobuyoshi Akimitsu.
  • Journal Title: BMC Genomics Volume: 16 Issue: 1 Pages: 154-154
  • DOI: 10.1186/s12864-015-1358-y
  • Peer Reviewed / Open Access
• [Journal Article] Genome-Wide Analysis of Long Noncoding RNA Turnover (2015)
  • Author(s): Hidenori Tani, Naoto Imamachi, Rena Mizutani, Katsutoshi Imamura, Yeondae Kwon, Satoru Miyazaki, Sho Maekawa, Yutaka Suzuki, Nobuyoshi Akimitsu
  • Journal Title: Nuclear Bodies and Noncoding RNAs: Methods and Protocols Volume: 1262 Pages: 305-320
  • Peer Reviewed
• [Presentation] Loss of RNA degradation factors upon Salmonella infection stabilizes nuclear long non-coding RNAs involving antibacterial response (2017)
  • Author(s): Imamura K
  • Organizer: The Start of New Genomics
  • Place of Presentation: 伊藤国際学術研究センター、東京
  • Year and Date: 2017-01-10
  • Int'l Joint Research
• [Presentation] サルモネラ感染に対する核内 RNA 分解機構による応答 (2017)
  • Author(s): 今村亮俊
  • Organizer: 第19回 日本RNA学会年会
• [Presentation] Loss of RNA degradation factors upon Salmonella infection stabilizes nuclear long non-coding RNAs involving antibacterial response (2017)
  • Author(s): Katsutoshi Imamura
  • Organizer: EMBO Conference Eukaryotic RNA turnover
  • Int'l Joint Research
• [Presentation] Functional analysis of long noncoding RNAs induced by Salmonella infection (2016)
  • Author(s): 今村亮俊
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2016-03-23