2021 Fiscal Year Final Research Report
DNA plasticity and RNA engrams by G-quadruplexes
| Project/Area Number |
20K21400
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | グアニン四重鎖 / RNA高次構造 / 神経機能 / ストレス顆粒 |
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| Outline of Final Research Achievements |
Sequences within RNA that are rich in consecutive guanine residues can adopt quadruple-stranded structures, RNA G-quadruplexes (G4RNAs). G4RNAs have profound implications for RNA metabolism, and prolonged disequilibrium of G4RNA formation is associated with neurodegeneration. Although G4RNA-forming sequences are abundant in transcriptomes, the comprehensive roles of G4RNAs remain poorly understood. Here we demonstrate that a newly identified G4RNA-binding protein undergoes G4RNA-dependent phase separation and contributes to the assembly of stress granules (SGs), a cellular phase-separated compartment. Importantly, we showed that G4-forming mRNAs undergo phase separation in a G4 structure-dependent manner, thereby coordinating SG assembly in cells. Consistent with these results, the bioinformatics approach revealed that G4-forming mRNAs are significantly enriched within SGs compared with non-G4 mRNAs. Cumulatively, G4RNA-dependent phase separation plays a critical role in SG assembly.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
研究代表者は、未だ生物学的機能が不明である「グアニン四重鎖」に着目し研究を行っている。グアニン四重鎖はグアニンが豊富な配列領域でDNA・RNAが形成する特殊な核酸高次構造のひとつである。しかしながら、mRNAグアニン四重鎖と「精神疾患の認知障害」との関連性は未だ詳細に明らかにされていない。本研究では、グアニン四重鎖を形成し、神経機能維持のために必要なタンパク質をコードするmRNA群と神経細胞に高発現する新たなグアニン四重鎖結合タンパク質を同定した。それらはストレス顆粒の形成に重要であり、神経細胞死に関与することが本研究により明らかになった。
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