非编码删除将Maenli lncRNA确定为特定于肢体的En1调节器
Lila Allou1,2, Sara Balzano3,4, Andreas Magg1,2,5
1RG Development & Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nature
|February 11, 2021
概括
长非编码RNA (lncRNA) 位点的遗传缺陷会导致人类严重的肢体形. 这项研究确定了Maenli lncRNA
科学领域:
- 遗传学
- 发育生物学
- 分子生物学
背景情况:
- 长非编码RNAs (lncRNAs) 越来越多地被认可为它们在基因调节中的作用.
- 它们对人类孟德尔病的具体参与仍然很大程度上没有特征.
- 肢体先天性缺陷代表着一个具有不同遗传病因的显著发育障碍群.
研究的目的:
- 研究 lncRNA 位点在人类孟德尔病的作用.
- 为了确定特定的复杂肢体形的遗传原因.
- 阐明新型 lncRNA 在肢体发育中的功能机制.
主要方法:
- 全基因组测序以确定肢体形患者的缺失.
- 在小鼠模型中重新设计已识别的删除.
- 在成长中的小鼠肢体中进行全基因组转录组分析 (RNA-seq).
- 在体内对 lncRNA 的功能研究.
主要成果:
- 在患有中体缩短,突触性和背部双症的患者中,发现了engrailed-1 (EN1) 基因上游的同卵性缺失.
- 经过重新工程删除的小鼠模型表现出En1表达的丧失以及与人类病例相似的双脊肢表型.
- 发现并命名Maenli lncRNA,对于cis的特定En1激活至关重要.
- 主转录活动对于调节肢体背腹极性至关重要.
结论:
- 由于Maenli lncRNA局部的遗传切除导致了严重的孟德尔肢体形.
- 通过对En1进行调节, 控制四肢发育的基因调节网络.
- 这项研究强调了 lncRNAs 在人类发育障碍中的关键作用, 并确定了 Maenli 作为肢体模式的关键参与者.
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