基于CRISPR-Cas9的非传统转化体的功能性询问揭示了人类癌症对神秘的非正统的开放阅读框架的依赖
Caishang Zheng1, Yanjun Wei1, Peng Zhang1,2
1Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nature structural & molecular biology
|November 6, 2023
概括
研究人员发现了一种神秘的微蛋白,SMIMP,通过影响基因调节来促进结直肠癌 (CRC). 这一发现突出显示了电力市场的潜力.
科学领域:
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
- 癌症生物学 癌症生物学
背景情况:
- 除了注释的翻译组之外的神秘翻译产生功能性蛋白质.
- 隐秘的非正规的开放阅读框架 (ORF) 在癌症中的作用在很大程度上是未知的.
- 结肠直肠癌 (CRC) 提供了一个研究这些神秘的ORF的机会.
研究的目的:
- 系统地确定结直肠癌对非正典ORF的依赖性.
- 研究CRC中微蛋白SMIMP的功能和机制.
- 探索"黑暗"蛋白质组的治疗和诊断潜力.
主要方法:
- 综合性的多原子策略,结合了核糖体分析和CRISPR-Cas9淘汰查.
- 对结直肠癌的分子和临床数据进行大规模分析.
- 在体内验证促进瘤功能和机制研究.
主要成果:
- 许多非正典的ORF在CRC上调并与预后不佳有关.
- 在CRC中,由灵长类动物特有的长非编码RNA编码的微蛋白SMIMP被提升.
- SMIMP与凝聚素亚单元SMC1A相互作用,促进瘤抑制剂CDKN1A和CDKN2B的表观遗传抑制.
结论:
- 像SMIMP这样的神秘微蛋白是凝聚蛋白介导基因调节中的关键参与者.
- "黑暗"蛋白质组源于神秘的非正典ORF,为癌症提供了潜在的治疗和诊断点.
- 这项研究揭示了对结直肠癌病原发生的新见解,并突出了尚未探索的蛋白质组景观.
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