SON protein regulates GATA-2 through transcriptional control of the microRNA 23a~27a~24-2 cluster
| Autor: | Erin Eun Young Ahn, Wei-Jong Shia, Miao Chia Lo, Tsunehito Higashi, Russell Dekelver, Ming Yan, Christopher J. Hickey, Dong-Er Zhang, Shinobu Matsuura |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Cellular differentiation RNA Splicing Biology Biochemistry Models Biological Minor Histocompatibility Antigens Mice Transcription (biology) microRNA Transcriptional regulation medicine Animals Humans Gene Regulation RNA Messenger Promoter Regions Genetic Molecular Biology Transcription factor 3' Untranslated Regions Regulation of gene expression Gene knockdown Hematopoietic stem cell Cell Differentiation Cell Biology U937 Cells Molecular biology humanities Hematopoiesis Up-Regulation DNA-Binding Proteins GATA2 Transcription Factor Mice Inbred C57BL Leukemia Myeloid Acute MicroRNAs medicine.anatomical_structure Gene Expression Regulation K562 Cells |
| Zdroj: | The Journal of biological chemistry. 288(8) |
| ISSN: | 1083-351X |
| Popis: | SON is a DNA- and RNA-binding protein localized in nuclear speckles. Although its function in RNA splicing for effective cell cycle progression and genome stability was recently unveiled, other mechanisms of SON functions remain unexplored. Here, we report that SON regulates GATA-2, a key transcription factor involved in hematopoietic stem cell maintenance and differentiation. SON is highly expressed in undifferentiated hematopoietic stem/progenitor cells and leukemic blasts. SON knockdown leads to significant depletion of GATA-2 protein with marginal down-regulation of GATA-2 mRNA. We show that miR-27a is up-regulated upon SON knockdown and targets the 3′-UTR of GATA-2 mRNA in hematopoietic cells. Up-regulation of miR-27a was due to activation of the promoter of the miR-23a∼27a∼24-2 cluster, suggesting that SON suppresses this promoter to lower the microRNAs from this cluster. Our data revealed a previously unidentified role of SON in microRNA production via regulating the transcription process, thereby modulating GATA-2 at the protein level during hematopoietic differentiation. |
| Databáze: | OpenAIRE |
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