Sequence and structure of ncRNA operation elements

2018 Fiscal Year Final Research Report

• Project Area: Neo-taxonomy of noncoding RNAs
• Project/Area Number: 26113002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hokkaido University
• Principal Investigator: Hirose Tetsuro 北海道大学, 遺伝子病制御研究所, 教授 (30273220)
• Co-Investigator(Kenkyū-buntansha): 富田 耕造 東京大学, 大学院新領域創成科学研究科, 教授 (00345274)
• Project Period (FY): 2014-07-10 – 2019-03-31
• Keywords: noncoding RNA / 核内構造 / 液相分離 / ゲノム機能 / RNP複合体

Outline of Final Research Achievements

This study investigated the operating elements and machinery of arcRNAs that build massive intracellular structures. NEAT1 was employed as a model arcRNA. The operating elements were identified by the analyses using genome editing technology and revealed that ncRNA is comprised of modular domain structure such as those in polypeptides. It also revealed that multiple prion-like proteins bind the operating elements and induce liquid-liquid phase separation that eventually form a massive structure. A new method for searching arcRNAs has been developed and showed that the human genome produces numerous arcRNAs, suggesting that arcRNA can be a distinct taxon of ncRNAs. Furthermore, the structural analysis of the ncRNA processing factors revealed the detail molecular process at the atomic level.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ncRNA配列中の作動エレメントと作動装置の解析を、世界に先駆けて詳細に行ったものであり、ncRNAの機能構造の理解に大きく貢献した。また一方で、ncRNA作動エレメントの機能として、プリオン様タンパク質を介した液相分離の誘発という作動原理を明確に示すことができ、ncRNA研究と相分離研究の接点を見いだしたことにより分子細胞生物学分野に大きなインパクトを与えた。また新規arcRNA探索法の開発によって、上記arcRNA機能の一般性が示され、arcRNAをncRNAの独立タクソンとして提唱するに至った。