长非编码RNACRNDE中的一种超保守的snoRNA类元素促进了核糖体生物发生和细胞增殖
Jong-Sun Lee1, Tu Dan2, He Zhang3
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
一种新的长非编码RNA,CRNDE-UCE,通过促进60S核糖体生物发生,对细胞癌 (RCC) 细胞增殖至关重要. 这一发现揭示了癌症中非编码RNA的新机制.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 在RNA生物学,RNA生物学.
背景情况:
- 癌细胞需要增加核糖体的生产,以便快速增殖.
- 小核RNAs (snoRNAs) 是已知的核糖体生物发生的调节者.
- 其他非编码RNA,如长非编码RNA (lncRNA) 在核糖体生产中的作用不太清楚.
研究的目的:
- 为了确定参与细胞癌 (RCC) 细胞增殖的必不可少的 lncRNA.
- 阐明已识别的 lncRNA 在核糖体生物生成中的功能.
主要方法:
- 克里斯普尔干扰 (CRISPRi) 选被用于识别RCC细胞中必不可少的lncRNAs.
- 进行了细胞下定位和功能测试,以描述lncRNA的作用.
- 研究了lncRNA,rRNA和蛋白质因子之间的生化相互作用.
主要成果:
- 一种替代拼接的lncRNA异型,CRNDE-UCE,被确定为RCC细胞增殖的关键.
- CRNDE-UCE定位在核细胞中,并促进60S核糖体子单元生物发生.
- 在CRNDE-UCE中,超保存元素 (UCE) 作为未经处理的C/D盒斯诺RNA,与rRNA相互作用,并促进60S生物发生因子eIF6.6的招募.
结论:
- lncRNA CRNDE-UCE通过增强RCC中的核糖体生产来支持瘤发生起着至关重要的作用.
- CRNDE-UCE 的 UCE 区域表现出功能多功能性,作为 snoRNA 调节核糖体生物发生.
- 这些发现扩大了参与核糖体生物发生的已知非编码RNA的范围,并为癌症提供了潜在的治疗点.
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