替代性转录重新编码人类基因以表达重叠的,框架移动的微蛋白质
Haomiao Su1,2, Samuel G Katz3, Sarah A Slavoff1,2,4
1Department of Chemistry, Yale University, New Haven, CT 06520, USA.
bioRxiv : the preprint server for biology
|November 1, 2024
概括
人类基因可以通过替代转录来表达来自内部开放阅读框架 (iORF) 的隐藏微蛋白. 这一发现揭示了人类转录组和蛋白质组的新复杂性,挑战了以前关于基因表达的假设.
科学领域:
- 基因组学和转录基因组学
- 分子生物学分子生物学
- 人类基因表达方式
背景情况:
- 内部开放式阅读框架 (iORFs) 之前被认为在人类基因组中很少见.
- 人类iORFs的功能意义和表达在很大程度上仍未被描述.
- 标注编码序列 (CDS) 被认为是人类基因的主要功能单位.
研究的目的:
- 调查功能性人类iORFs的存在和表达.
- 开发用于识别和验证来自替代转录的iORF表达的方法.
- 探索iORF表达对基因活动的功能影响.
主要方法:
- 开发一种新的生物信息学管道,用于将翻译的iORF分配给替代的转录.
- 利用长读测序进行转录基因分析和验证.
- 进行了分子验证实验,以确认人类基因中的iORF表达.
主要成果:
- 确定了数百个案例,其中替代转录重新编程人类基因以表达iORF编码的微蛋白.
- 证明了许多非编码替代转录的注释很差,但可以导致iORF翻译.
- 通过测序和分子技术验证了众多人类iORFs的表达.
- 展示了一种保存的DEDD2iORF,该iORF改变了基因功能,从亲亡的转变为反亡的.
结论:
- 替代性转录变异通过使iORF表达能够显著扩大人类基因组的编码潜力.
- 这种机制揭示了人类转录组和蛋白质组中以前未知的复杂层.
- iORF表达可以功能性地重编程基因,以DEDD2基因为例.
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