Mechanisms of tissue-specific pre-mRNA processing(Fostering Joint International Research)

• Project/Area Number: 15KK0252
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KUROYANAGI Hidehito 東京医科歯科大学, 難治疾患研究所, 准教授 (30323702)
• Research Collaborator: Black Douglas L. カリフォルニア大学ロサンゼルス校, MIMG, Professor ; XING Yi ; ONO Shoichiro
• Project Period (FY): 2016 – 2018
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 遺伝子発現制御 / RNAプロセシング / 線虫 / 新生RNA / 転写 / mRNA前駆体 / イントロン / 次世代シーケンサー / RNAseq

Outline of Final Research Achievements

We utilized C. elegans as a model organism to analyze temporal patterns of pre-mRNA processing genome wide. We determined the half-lives of each intron as well as of each mRNA in living multicellular organism. The half-lives vary from less than one minute to more than hours. We determined features of introns/mRNAs that correlated with the half-lives. This fundamental information about the dynamics of pre-mRNA processing will help understanding regulation mechanisms for tissue-specific alternative processing in C. elegans and higher organisms.

Academic Significance and Societal Importance of the Research Achievements

多細胞生物は1つの遺伝子からmRNA前駆体のプロセシング（加工）方法を変化させることで多様なmRNAひいては多様なタンパク質を作っている。しかし、mRNAの加工パターンが多様であることは明らかになっていたが、加工の進行過程におけるmRNA前駆体の経時変化については、ほとんど解析されていなかった。本研究により個々のイントロンの除去など各プロセシング段階の速度が個体レベルでゲノムワイドに明らかになったことで、組織的特異的にmRNAを作り分ける過程やその制御のしくみの解明がより一層進むと期待される。

Research Products

• [Int'l Joint Research] カリフォルニア大学ロサンゼルス校(米国) (2017)
• [Journal Article] Alternative splicing of the Caenorhabditis elegans lev-11 tropomyosin gene is regulated in a tissue-specific manner (2018)
  • Author(s): Watabe Eichi、Ono Shoichiro、Kuroyanagi Hidehito
  • Journal Title: Cytoskeleton Volume: 75 Issue: 10 Pages: 427-436
  • DOI: 10.1002/cm.21489
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization (2018)
  • Author(s): Rie Murayama, Mariko Kimura-Asami, Marina Togo-Ohno, Yumiko Yamasaki-Kato, Taeko K. Naruse, Takeshi Yamamoto, Takeharu Hayashi, Tomohiko Ai, Katherine G. Spoonamore, Richard J. Kovacs, Matteo Vatta, Mai Iizuka, Masumi Saito, Shotaro Wani, Yuichi Hiraoka, Akinori Kimura & Hidehito Kuroyanagi
  • Journal Title: Scientific Reports Volume: 印刷中 Issue: 1 Pages: 8970-8983
  • DOI: 10.1038/s41598-018-26624-w
  • NAID: 120007031665
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematode Caenorhabditis elegans (2018)
  • Author(s): Barnes Dawn E.、Watabe Eichi、Ono Kanako、Kwak Euiyoung、Kuroyanagi Hidehito、Ono Shoichiro
  • Journal Title: Molecular Biology of the Cell Volume: 29 Issue: 9 Pages: 1075-1088
  • DOI: 10.1091/mbc.e17-03-0152
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alternative Splicing Regulator RBM20 and Cardiomyopathy (2018)
  • Author(s): Watanabe Takeshi、Kimura Akinori、Kuroyanagi Hidehito
  • Journal Title: Frontiers in Molecular Biosciences Volume: 5 Pages: 105-105
  • DOI: 10.3389/fmolb.2018.00105
  • NAID: 120007150215
  • Peer Reviewed / Open Access
• [Journal Article] An emerging model organism Caenorhabditis elegans for alternative pre-mRNA processing in vivo (2017)
  • Author(s): Shotaro Wani & Hidehito Kuroyanagi
  • Journal Title: Wiley Interdisciplinary Reviews: RNA Volume: 印刷中 Issue: 6
  • DOI: 10.1002/wrna.1428
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] トロポミオシンをコードするlev-11遺伝子の選択的スプライシング制御 (2019)
  • Author(s): 黒柳秀人
  • Organizer: 東京地区線虫勉強会
• [Presentation] 動物個体におけるmRNA前駆体プロセシング動態の解析 (2018)
  • Author(s): 渡部栄地，黒柳秀人
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] Genome-wide Kinetic Analysis of Pre-mRNA Processing in Living Animals (2018)
  • Author(s): 渡部栄地，黒柳秀人
  • Organizer: 線虫研究の未来を創る会
• [Presentation] Genome-Wide Kinetic Analysis of Pre-mRNA Processing in Living Animals (2018)
  • Author(s): 渡部栄地
  • Organizer: 東京地区線虫勉強会
• [Presentation] C. elegans代謝関連遺伝子のスプライシング制御における食餌の影響 (2018)
  • Author(s): 和仁翔太郎
  • Organizer: 東京地区線虫勉強会
• [Presentation] Phosphorylation of an RNA-binding protein RBM20 on an RSRSP stretch, whose missense mutations cause familial dilated cardiomyopathy, is required for proper nuclear localization and splicing regulation (2017)
  • Author(s): Rie Murayama, Mariko Kimura, Yumiko Yamasaki-Kato, Mai Iizuka, Marina Togo-Ohno, Hidehito Kuroyanagi
  • Organizer: The 22nd Annual Meeting of the RNA Society
  • Int'l Joint Research
• [Presentation] 個体レベルで行うmRNA前駆体プロセシングの動態の解析 (2017)
  • Author(s): 渡部栄地、黒柳秀人
  • Organizer: 第19回日本RNA学会年会
• [Presentation] C. elegans代謝関連遺伝子のスプライシング制御における食餌の影響 (2017)
  • Author(s): 和仁翔太郎、黒柳秀人
  • Organizer: 第19回日本RNA学会年会
• [Presentation] Genome-wide kinetic analysis of pre-mRNA processing in living animals (2017)
  • Author(s): Eichi Watabe, Hidehito Kuroyanagi
  • Organizer: CSHL Meeting on 40 YEARS OF mRNA SPLICING: FROM DISCOVERY TO THERAPEUTICS
  • Int'l Joint Research
• [Presentation] 個体レベルで行う mRNA前駆体プロセシングの動態の解析 (2017)
  • Author(s): 渡部栄地、黒柳秀人
  • Organizer: ConBio2017（2017年度生命科学系学会合同年次大会）
• [Book] 遺伝子発現制御機構 (2017)
  • Author(s): 田村隆明、浦聖惠（編）
  • Total Pages: 264
  • Publisher: 東京化学同人
  • ISBN: 9784807909179
• [Remarks] 東京医科歯科大学難治疾患研究所フロンティア研究室遺伝子発現制御学
• [Remarks] 東京医科歯科大学 難治疾患研究所 遺伝子発現制御学
  • URL: http://www.tmd.ac.jp/end/
• [Remarks] 新学術領域研究「ノンコーディングRNAネオタクソノミ」研究成果紹介
  • URL: https://ncrna.jp/blog/item/370-rouge
• [Remarks] みらいぶプラス
  • URL: https://www.milive-plus.net/newleader/049/