Integrated analysis of selective mRNA export by mRNA export factors, UAP56 and URH49

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K15807
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Fujita Health University (2020); Kyoto University (2019)
• Principal Investigator: fujita ken-ichi 藤田医科大学, 総合医科学研究所, 助教 (70816884)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 選択的mRNA輸送 / 結晶構造解析 / トランスクリプトーム解析

Outline of Final Research Achievements

For the expression of protein, genome information is transcribed to pre-mRNA in the nucleus. Pre-mRNA undergoes processing to be maturated mRNA. Then mRNA is exported to the cytoplasm for protein translation. In human, closely related RNA helicases, UAP56 and URH49, form distinct TREX and AREX complexes, respectively. Either TREX or AREX promotes selective mRNA export of a particular set of mRNAs. However, the underlying mechanism of mRNA recognitions in association with the distinct complexes remains poorly understood. We have analyzed the structures of UAP56 and URH49, as well as mutants in which regions important for complex formation were replaced, and found that the structural difference between UAP56 and URH49 is important for the difference in complex formation. In addition, we demonstrate that mRNA export regulated by UAP56 and URH49 were achieved during splicing step.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

近年、細胞分化、多分化能維持、ゲノム安定性、ウイルスRNA制御、多発性硬化症の発症において、UAP56とURH49による選択的mRNA輸送の関与が報告されている。よって本研究のUAP56とURH49によるmRNA核外輸送機構の解明は、様々な生命現象や病気の理解に大きく貢献するだけでなく、その制御に向けた基盤となることが期待される。