Elucidation of circRNA transport pathway

• Project/Area Number: 18K05563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Setsunan University (2020-2021); Fujita Health University (2018-2019)
• Principal Investigator: Yoshimoto Rei 摂南大学, 農学部, 講師 (70595652)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: RNA / 環状RNA / circRNA / スプライシング / 輸送 / 核外輸送 / RNAプロセシング

Outline of Final Research Achievements

ASO inhibition experiments using human neuroblastoma (SH-SY5Y) cells expressing ciRS-7 have revealed the presence of a complementary sequence in the ciRS-7 intron that is required for cyclization. Bioinformatics analysis and reporter experiments revealed that a repeat sequence called MIR (Mammalian Interspersed Repeats) (SINE) is required for circularization. Furthermore, we discovered many circRNAs produced in an MIR-dependent manner by analyzing RNA-Seq data, and established that MIR-dependent circularization that is highly conserved from mouse to human.

Academic Significance and Societal Importance of the Research Achievements

circRNAのほとんどは細胞質に局在し、主な機能としては①マイクロRNA(miRNA)を吸着することによりmiRNAの転写後発現調節を制御するもの、②RNA結合タンパク質(RBP)の機能を制御するもの、そして③mRNA由来の翻訳枠(ORF)を持ち翻訳を受けるものが存在する(図1)。したがってcircRNAはマイクロRNA(miRNA)や長鎖ノンコーディングRNA(lncRNA)に並ぶ新たな機能性RNA群であり、circRNAの機能解明は、重要な疾患の治療に貢献できる。

Research Products

• [Int'l Joint Research] Helmholtz Zentrum Munchen(ドイツ)
• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] Aarhus University(デンマーク)
• [Journal Article] SPF45/RBM17-dependent, but not U2AF-dependent, splicing in a distinct subset of human short introns (2021)
  • Author(s): Fukumura Kazuhiro、Yoshimoto Rei、Sperotto Luca、Kang Hyun-Seo、Hirose Tetsuro、Inoue Kunio、Sattler Michael、Mayeda Akila
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 1-12
  • DOI: 10.1038/s41467-021-24879-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spliceostatin A interaction with SF3B1 limits U1 snRNP availability and causes premature cleavage and polyadenylation. (2021)
  • Author(s): Yoshimoto, R., Chhipi-Shrestha, J.K., Schneider-Poetsch, T., Furuno, M., Burroughs, A.M., Noma, S., Suzuki, H., Hayashizaki, Y., Mayeda, A., Nakagawa, S., Kaida, D., Iwasaki, S., Yoshida, M.
  • Journal Title: Cell Chem. Biol. Volume: - Issue: 9 Pages: 1356-1365
  • DOI: 10.1016/j.chembiol.2021.03.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Biosynthesis of Circular RNA ciRS-7/CDR1as Is Mediated by Mammalian-wide Interspersed Repeats (2020)
  • Author(s): Yoshimoto Rei、Rahimi Karim、Hansen Thomas B.、Kjems J?rgen、Mayeda Akila
  • Journal Title: iScience Volume: 23 Issue: 7 Pages: 101345-101345
  • DOI: 10.1016/j.isci.2020.101345
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants (2020)
  • Author(s): Kawamoto Takahito、Yoshimoto Rei、Taniguchi Ichiro、Kitabatake Makoto、Ohno Mutsuhito
  • Journal Title: Genes to Cells Volume: 26 Issue: 1 Pages: 18-30
  • DOI: 10.1111/gtc.12817
  • Peer Reviewed / Open Access
• [Journal Article] Component of splicing factor SF3b plays a key role in translational control of polyribosomes on the endoplasmic reticulum (2019)
  • Author(s): Ueno Tomonori、Taga Yuki、Yoshimoto Rei、Mayeda Akila、Hattori Shunji、Ogawa-Goto Kiyoko
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 116 Issue: 19 Pages: 9340-9349
  • DOI: 10.1073/pnas.1901742116
  • Peer Reviewed / Open Access
• [Journal Article] The functional circular RNA, ciRS-7 (CDR1as), is biosynthesized using back-splicing promoted by inverted mammalian-wide MIRs but not primate-specific Alus (2018)
  • Author(s): Yoshimoto Rei、Rahimi Karim、Ebbesen Karoline K、Hansen Thomas、Kjems Jorgen、Mayeda Akila
  • Journal Title: biorxiv Volume: - Pages: 411231-411231
  • DOI: 10.1101/411231
  • Open Access / Int'l Joint Research
• [Presentation] A subset of human circRNAs are biosynthesized using mammalian-wide interspersed repeats (MIRs) and exported to cytoplasm via TAP/p15 pathway (2019)
  • Author(s): Rei Yoshimoto, Ichiro Taniguchi, Karim Rahimi, Jorgen Kjems, Thomas B. Hansen, Mutsuhito Ohno, Akila Mayeda.
  • Organizer: Eukaryotic mRNA Processing, CSHL
  • Int'l Joint Research
• [Presentation] ciRS-7 Is Biosynthesized Using Back-Splicing Promoted by Inverted MIR Elements And Is Exported to Cytoplasm via Tap/p15 pathway (2018)
  • Author(s): Rei Yoshimoto, Ichiro Taniguchi, Ohno Mutsuhito and Akila Mayeda
  • Organizer: RNA Biology, Cold Spring Harbor Asia
  • Int'l Joint Research
• [Remarks] スプライシング調節化合物がもたらす新たな作用を発見
  • URL: https://www.riken.jp/press/2021/20210330_1/index.html
• [Remarks] タンパク質の設計図であるメッセンジャーRNAから 短い不必要断片を取り除く新しい因子の発見
  • URL: https://www.fujita-hu.ac.jp/news/j93sdv000000b36n.html