Elucidation of the molecular function of Ahed, a nuclear protein that controls proliferation and differentiation of epidermal keratinocytes.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08773
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kochi University
• Principal Investigator: Takaishi Mikiro 高知大学, 教育研究部医療学系臨床医学部門, 助教 (10303223)
• Co-Investigator(Kenkyū-buntansha): 佐野 栄紀 高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 皮膚 / 表皮 / 角化細胞 / RNAスプライシング / スプライソソーム

Outline of Final Research Achievements

In this study, to clarify molecular function of the gene, interacting proteins with Ahed were identified with co-immunoprecipitation and mass-spectrometry. As the result, some nuclear proteins including spliceosomal proteins were identified. In vitro protein synthesis and immunoprecipitation confirmed that some spliceosomal proteins were directly interacted with Ahed. Involvement of Ahed in RNA splicing was investigated with full-length cDNA-seq and found unique splicing isoforms were produced in the Ahed KO keratinocytes. Our findings indicate a novel spliceosomal protein Ahed has indispensable roles in cell proliferation of epidermal cells as well as hematopoietic cells by regulating RNA splicing.

Free Research Field

皮膚科学、細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究によりAhedは新規のRNAスプライシング制御因子であることが明らかになった。Ahedは多様な臓器で発現していることが明らかになっているので、表皮、造血細胞のみならず様々な細胞系譜で重要な役割を担っていることが示唆される。近年がんをはじめとする様々な疾患にスプライシング関連因子の遺伝子変異が見つかっている。データーベースによれば、いくつかのがんでAhedの遺伝子変異が見つかる。更なる研究により、がんにおけるAhedの関わりが明らかとなれば社会的意義は大きいと考えられる。