In silico search and functional analysis for genes having differentially localized protein isoforms via alternative splicing and alternative translation initiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K11543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Kenichiro Imai 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (80442573)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: アイソフォーム / 細胞内局在 / ターゲッティングシグナル予測 / 多機能性 / 選択的スプライシング / 選択的翻訳開始点

Outline of Final Research Achievements

In humans, most genes produce multiple isoforms via alternative splicing or alternative translation initiation. Several cases are known in which isoforms of the same gene exhibit change of localization to regulate cellular function. However, the precise number of genes having differentially localized protein isoforms produced from the human genome is still unknown. Thus, we explored genes having differentially localized protein isoforms based on prediction of gain or loss of N-terminal targeting signals; mitochondrial targeting signal (MTS) and ER signal peptide (SP). We found about 60% of predicted genes containing MTS are possibility to change localization sites at isoform level (741 genes) while about 30% might change localization sites in predicted genes containing SP (1055 gene). Furthermore, we found more than a dozen of promising candidates of differentially localized protein isoforms by analysis of structure, function, and transcript expression of the protein isoforms.

Free Research Field

バイオインフォマティクス

Academic Significance and Societal Importance of the Research Achievements

遺伝子の重要な機能調節として、選択的スプライシングや選択的翻訳開始点によりN末端のターゲッティングシグナルの欠損/獲得による細胞内局在の変化とそれに伴う機能調節があるが、いったいどれほどの遺伝子が、どのような条件によって、このような細胞機能の調節を行うかは未だよくわかっていない。これに対し、本研究では、MTSの欠失/獲得よりアイソフォームレベルで局在変化を起こし、新たな機能調節を行う遺伝子候補を見出すことができた。今後、実験的検証を進めていくが、本研究で得られた成果は、アイソフォームレベルでの局在変化による機能調節機序の解明への重要なリソースとなると考えられる。