2018 Fiscal Year Final Research Report

New roles and mechanisms of translational regulation mediated by upstream open reading frame-encoded peptides

Research Project

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Project/Area Number	16K07387
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Plant molecular biology/Plant physiology
Research Institution	Hokkaido University
Principal Investigator	ONOUCHI HITOSHI 北海道大学, 農学研究院, 准教授 (50322839)
Research Collaborator	HAYASHI noriya UMEHARA shun-ichi SASAKI shun SASAHARA daiki
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	uORF / リボソーム / 翻訳制御 / 翻訳アレスト / 新生ペプチド
Outline of Final Research Achievements	Upstream open reading frames (uORFs) are small ORFs located in the 5′ untranslated regions (5′-UTRs) of many eukaryotic mRNAs. Some uORFs encode regulatory peptides that repress translation of the downstream main ORF. Most of the previously characterized uORFs encoding regulatory peptides play a role in feedback regulation in response to a metabolite. To identify new physiological roles of uORF-encoded regulatory peptides, we searched for uORFs encoding regulatory peptides among angiosperm uORFs with evolutionarily conserved amino acid sequences, and identified nine novel regulatory uORFs. We investigated physiological roles and mechanisms of the translational regulation mediated by these uORFs. We identified a uORF encoding a peptide that causes ribosome stalling in response to magnesium and thereby represses main ORF translation under high magnesium conditions. In addition, we identified a uORF involved in translational regulation in response to nucleolar stress.
Free Research Field	分子生物学
Academic Significance and Societal Importance of the Research Achievements	本研究では、マグネシウムに応答してリボソームの停滞を引き起こし、それにより主要ORFの翻訳を抑制するuORFペプチドを見出した。これまでに代謝産物に応答してリボソームを停滞させるuORFペプチドは知られていたが、無機イオンに応答してリボソームを停滞させるuORFペプチドとしては、これが初めての発見である。また、核小体ストレスに応答して誘導される選択的スプライシングにより、uORFが除去されたmRNAが生産され、それによって主要ORFの翻訳が促進されるという、ストレスに応答した新たな翻訳制御機構を見出した。