DHFR2RNA直接调节二叶酸减少酶,其表达水平影响叶酸一碳代谢
Paola Drago1,2, Niamh Bookey1,2, Kit-Yi Leung3
1School of Biotechnology, Dublin City University, Dublin 9, Ireland.
概括
二叶酸还原酶 (DHFR) 活性对于一个碳代谢至关重要. 这项研究揭示了DHFR2RNA调节DHFR表达和活性,影响细胞叶酸代谢和 purin/pyrimidine合成.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞的新陈代谢
背景情况:
- 二叶酸减少酶 (DHFR) 对于一碳代谢至关重要,为核酸合成提供四叶酸.
- 线粒体DHFR活性以前归因于DHFR2,这是主要DHFR基因的对应物.
- 内源DHFR2蛋白通常是不可检测的,挑战其在线粒体活动中的作用.
研究的目的:
- 为了重新评估线粒体二酸盐还原酶活性的来源.
- 研究DHFR2在单碳新陈代谢中的作用.
- 通过DHFR2.2阐明DHFR活动的调节机制.
主要方法:
- 使用了具有调节DHFR和DHFR2表达的HepG2细胞系.
- 对DHFR和DHFR2进行了基因淘汰和淘汰实验.
- 分析了二叶酸还原酶活性,10-甲基四叶酸水平,以及相关酶的mRNA/蛋白质丰度.
主要成果:
- 确定的DHFR,而不是DHFR2,是线粒体二酸盐还原酶活性的主要来源.
- DHFR2RNA通过影响DHFR表达和活性,显著影响一个碳代谢.
- 脱离DHFR2导致DHFR活性降低,10-甲基四基酸盐减少,并降低DHFR,血清氧甲基转移酶和甲基基酸盐合成酶的调节.
- 再组合DHFR2恢复了DHFR水平,而DHFR倒置增加了DHFR2RNA.
结论:
- DHFR2很可能编码一个调节性RNA分子,而不是一个功能性蛋白质.
- 通过调节DHFR mRNA和蛋白质水平,DHFR2 RNA调节细胞二叶酸减少酶的活性.
- 这一发现重新定义了单碳新陈代谢和叶酸平衡的监管网络.
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