| 项目编号 | PRJCA024306 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 项目标题 | YTHDF2/3 are required for somatic reprogramming through different RNA deadenylation pathways | ||||||||||
| 涉及领域 | Medical | ||||||||||
| 数据类型 | Raw sequence reads | ||||||||||
| 物种名称 | Mus musculus | ||||||||||
| 描述信息 | N6-methyladenosine (m6A), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex. Ythdf2/3 deficiency further represses mesenchymal-to-epithelial transition (MET) and chromatin silencing at loci containing the TEAD motif, contributing to decreased reprogramming efficiency. Moreover, RNA interference of Tgfb1 or the Hippo signaling effectors Yap1, Taz, and Tead2 rescues Ythdf2/3-defective reprogramming. Overall, YTHDF2/3 couple RNA deadenylation and regulation with the clearance of somatic genes provides insights into iPSC reprogramming at the posttranscriptional level. | ||||||||||
| 样品范围 | Monoisolate | ||||||||||
| 发布日期 | 2024-03-20 | ||||||||||
| 出版信息 |
|
||||||||||
| 项目资金来源 |
|
||||||||||
| 提交者 | Jiekai Chen (chen_jiekai@gibh.ac.cn) | ||||||||||
| 提交单位 | Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences | ||||||||||
| 提交日期 | 2024-03-14 |