Ribosome quality control via intron-containing tRNA (ic-tRNA) in budding yeast

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K06491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: University of Hyogo
• Principal Investigator: HAYASHI Sachiko 兵庫県立大学, 理学研究科, 特任助教 (40791869)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: tRNA / イントロン / リボソーム / 翻訳 / 酵母

Outline of Final Research Achievements

The biological significance of introns in tRNA genes is still obscure. This study analyzed the impact of tRNA intron-deletion mutants in budding yeast on the general ribosomal quality control pathway. The deletion of introns from tRNA genes, particularly those that charge leucine (Leu) and have the anticodon CAA, suppressed ribosome stalling, which usually activates the ribosome-associated quality control (RQC) mechanism. This suppression led to an increase in aberrant translation. Furthermore, some of the translation products resulting from this aberrant translation formed aggregates in the cytoplasm, losing their functionality.

Free Research Field

分子生物学、生化学、遺伝学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

従来、翻訳異常や異常タンパク質の産生は、リボソームによる翻訳速度の低下やmRNA上の異常なコドンの読み枠による影響、tRNAアミノアシル化状態や分子シャペロン等の翻訳補助因子の量的・質的異常に主眼が置かれてきた。本研究は、ゲノム上のtRNAイントロンの有無という、これまで全く予想されて来なかった新たな局面からの異常が、一見、細胞内での全般的な翻訳を亢進させつつも、結果的には異常なタンパク質を産生、凝集体の集積を促すという、全く新しいプロテオスタシス異常のあり方を明らかにした。