論文 - 詳細
| RRC ID | 57179 |
|---|---|
| 著者 | Komori H, Golden KL, Kobayashi T, Kageyama R, Lee CY. |
| タイトル | Multilayered gene control drives timely exit from the stem cell state in uncommitted progenitors during Drosophila asymmetric neural stem cell division. |
| ジャーナル | Genes Dev |
| Abstract |
Self-renewal genes maintain stem cells in an undifferentiated state by preventing the commitment to differentiate. Robust inactivation of self-renewal gene activity following asymmetric stem cell division allows uncommitted stem cell progeny to exit from an undifferentiated state and initiate the commitment to differentiate. Nonetheless, how self-renewal gene activity at mRNA and protein levels becomes synchronously terminated in uncommitted stem cell progeny is unclear. We demonstrate that a multilayered gene regulation system terminates self-renewal gene activity at all levels in uncommitted stem cell progeny in the fly neural stem cell lineage. We found that the RNA-binding protein Brain tumor (Brat) targets the transcripts of a self-renewal gene, deadpan (dpn), for decay by recruiting the deadenylation machinery to the 3' untranslated region (UTR). Furthermore, we identified a nuclear protein, Insensible, that complements Cullin-mediated proteolysis to robustly inactivate Dpn activity by limiting the level of active Dpn through protein sequestration. The synergy between post-transcriptional and transcriptional control of self-renewal genes drives timely exit from the stem cell state in uncommitted progenitors. Our proposed multilayered gene regulation system could be broadly applicable to the control of exit from stemness in all stem cell lineages. |
| 巻・号 | 32(23-24) |
| ページ | 1550-1561 |
| 公開日 | 2018-12-1 |
| DOI | 10.1101/gad.320333.118 |
| PII | gad.320333.118 |
| PMID | 30463902 |
| PMC | PMC6295162 |
| MeSH | 3' Untranslated Regions / genetics Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Division / genetics* Cell Self Renewal / genetics* Co-Repressor Proteins / metabolism DNA-Binding Proteins / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / cytology Drosophila melanogaster / embryology* Drosophila melanogaster / genetics* Gene Expression Regulation, Developmental / genetics* Gene Silencing Neural Stem Cells / cytology* Nuclear Proteins / metabolism Stem Cells / cytology |
| IF | 8.99 |
| 引用数 | 2 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | |