核毛孔复合体的O-GlcNAc调制可以调节mRNA出口效率
Samuel L Junod1, Coby Rush1, Mark Tingey1
1Department of Biology, Temple University, Philadelphia, PA 19122.
概括
核毛孔复合体 (NPC) 的O-链接N-乙糖胺 (O-GlcNAc) 修饰调节信使RNA (mRNA) 的出口. 改变O-GlcNAc水平会影响NPC结构和mRNA出口效率,这表明核运输障碍的治疗潜力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 有效的基因表达依赖于通过核孔综合体 (NPC) 调节的mRNA输出.
- NPCs被O结合的N-乙糖胺 (O-GlcNAc) 广泛修饰,这是一个动态的翻译后修饰.
- 失调的O-GlcNAcylation与各种人类疾病有关,但其在NPC功能中的作用尚不清楚.
研究的目的:
- 调查O-GlcNAc在NPC中的精确分布.
- 量化O-GlcNAcylation水平对mRNA出口动态的影响.
- 探索改变O-GlcNAc修饰对NPC运输动态的功能影响.
主要方法:
- 使用单点边缘激发亚衍射 (SPEED) 显微镜和随机光学重建显微镜 (STORM).
- 在NPC中绘制了O-GlcNAc模拟物 (GlcNAz) 在纳米尺度上的分布.
- 量化mRNA-蛋白质复合体 (mRNP) 在不同的O-GlcNAcylation条件下出口动力学.
主要成果:
- 在低和高O-GlcNAcylation下,O-GlcNAc模拟 (GlcNAz) 的分布从NPC中央通道转移到外围.
- 改变的GlcNAz分布与mRNP局部化和核素组合的变化相关.
- 较高的O-GlcNAcylation提高了mRNA出口效率~61%,而较低的水平降低到~16%.
结论:
- O-GlcNAcylation可以动态调节NPC架构和运输.
- NPC O-GlcNAc水平是mRNA出口效率的关键调节者.
- 针对NPC O-GlcNAc可能为与核运输相关的疾病提供治疗策略.
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