'Poisoning' of the transcriptome by ultraconserved elements.
'Poisoning' of the transcriptome by ultraconserved elements.
复制标题
超保守元素对转录组的“中毒”。
DOI：
10.1038/s41580-022-00527-1
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Anczuków,Olga
中科院分区：
文献类型：
--
作者：
Leclair,NathanK;Anczuków,Olga
选择性RNA剪接允许单个基因编码不同的功能不同的RNA亚型，这些亚型在稳定性、定位和蛋白质编码潜力方面可能不同。这一关键过程受剪接因子的调控，剪接因子与特定的前-mRNA序列结合，通过核心剪接体增强或抑制剪接位点的识别。由于它们具有调节转录组的能力，SF水平受到严格调控，它们的失调会导致许多人类疾病。一种复杂的调控机制依赖于SF基因中超冷端元件(UCES)的选择性剪接。2004年首次在人类基因组中描述了一组UCES；UCES被定义为与大鼠和小鼠基因组完全序列同源的区域。这种显著的进化保守表明，UCE具有关键的生物学作用，然而，有趣的是，在小鼠模型中，UCE缺失没有明显的表型。
Alternative RNA splicing allows an individual gene to encode functionally distinct RNA isoforms that can differ in stability, localization and protein-coding potential. This key process is regulated by splicing factors (SF), which bind to specific pre-mRNA sequences and enhance or repress splice-site recognition by the core spliceosome. Given their ability to modulate the transcriptome, SF levels are tightly regulated and their dysregulation causes many human diseases. One complex regulatory mechanism relies on alternative splicing of ultraconserved elements (UCEs) in SF genes themselves.A set of UCEs in the human genome was first described in 2004; UCEs were defined as regions> 200bp in length with complete sequence homology to rat and mouse genomes. This remarkable evolutionary conservation suggested UCEs have crucial biological roles, yet, intriguingly, UCE deletions in mouse models had no obvious phenotypes.