蛋白序列编辑定义了SKN-1A/Nrf1和SKN-1C/Nrf2的独特和重叠的功能
Briar Jochim1, Irini Topalidou1, Nicolas Lehrbach1
1Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washinton, United States of America.
PLoS genetics
|July 7, 2025
概括
对SKN-1A/Nrf1的序列编辑对于蛋白质酶基因激活至关重要. 这一过程也影响了氧化还原和排毒基因,揭示了SKN-1A/Nrf1和SKN-1C/Nrf2在抗压力方面的不同作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞应激反应的应激反应
背景情况:
- Nrf/NFE2L转录因子家族调节关键细胞过程,包括还原氧平衡,解毒,新陈代谢,蛋白质稳定和衰老.
- Nrf1 (NFE2L1) 主要在压力下对蛋白质体基因进行上调,而Nrf2 (NFE2L2) 处理氧化应激反应和外源生物排毒.
- C. elegans的SKN-1基因编码了SKN-1A和SKN-1C异型,与哺乳动物的Nrf1和Nrf2相似,分别具有相同的DNA结合域,导致有关功能重叠和区分的问题.
研究的目的:
- 调查翻译后序列编辑对激活SKN-1A的转录输出的后果.
- 为了澄清SKN-1A/Nrf1和SKN-1C/Nrf2在细胞应激反应中的不同和重叠的功能.
- 了解序列编辑如何调节SKN-1A/Nrf1.1的调节作用.
主要方法:
- 使用具有特定突变等位基因的C. elegans模型来禁用SKN-1A或SKN-1C.
- 分析了响应激活SKN-1A的转录组变化,重点关注序列编辑的影响.
- 研究了PNG-1/NGLY1:N-糖酶在SKN-1A的翻译后修改中的作用.
主要成果:
- 证实了涉及PNG-1/NGLY1的序列编辑对于SKN-1A/Nrf1.1激活蛋白酶子单元基因至关重要.
- 证明编辑序列的SKN-1A/Nrf1可以激活氧化回归稳定和外来生物排毒基因,但在较小程度上比SKN-1C/Nrf2.
- 表明SKN-1A和SKN-1C异型单独通过不同的信号通路对氧化应激抵抗有所贡献.
结论:
- SKN-1A/Nrf1的序列编辑是一个关键的调控机制,它决定了其特定的转录基因标,特别是在蛋白质组基因中.
- 虽然SKN-1A/Nrf1和SKN-1C/Nrf2共享了一些目标基因,但序列编辑微调了SKN-1A/Nrf1的活动,导致了不同的功能结果.
- 这些发现阐明了翻译后修饰如何控制Nrf1和Nrf2在细胞应激适应中的特殊作用.
相关概念视频
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Exon Recombination
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Exon shuffling follows “splice frame rules.” Each exon has three reading...


