Molecular mechanism of functional conversion from noncoding to coding RNAs

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19293
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Hirose Tetsuro 大阪大学, 大学院生命機能研究科, 教授 (30273220)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: long noncoding RNA / mRNA / 核外輸送 / サテライトDNA / 相分離

Outline of Final Research Achievements

We analyzed the process by which HSATIII RNAs, which possess definitive lncRNA functions within the cell nucleus, relocate to the cytoplasm and convert its function to mRNA in response to thermal stress and recovery. Regarding the nuclear export of HSATIII RNA, we found that HSATIII RNA-binding proteins are remodeled and eventually the nuclear export factor ALY/REF binds to HSATIII RNA. This reassembly is promoted by the 'crucible' or 'sponge' functions of HSATIII. Next, stress granule factors and chaperones were detected as interactors of the HSATIII translation products. Furthermore, we confirmed that the translation products co-localize with these interactors at actin polymerization sites at the cell periphery.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、核から細胞質へのRNAの局在変化機構について、相分離構造体でのRNA機能が結合因子の再構築を促し、結果的に核外輸送因子を呼び込んでRNAを細胞質に輸送させるという流れが明らかになった。一方で、細胞質での翻訳産物の相互作用因子と細胞内局在が明らかになったことによって、機能転換したmRNAが機能的なポリペプチドを産生していることが示唆された。これによって、lncRNAからmRNAへの機能変換の全体像を把握し、前例のないRNAの複雑な一生を明らかにする道筋を整備できた。今後、このポリペプチド機能の解明によって、ストレス応答や関係する疾患の新たな機構解明につながる可能性が期待できる。