title: SON protein regulates GATA-2 through transcriptional control of the microRNA 23a~27a~24-2 cluster.
abstract: 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.
authors: Moores UCSD Cancer Center, the University of California San Diego, La Jolla, California 92093, USA.
authors: Erin Eun-Young
authors: EE
authors: Ahn
authors: Tsunehito
authors: T
authors: Higashi
authors: Ming
authors: M
authors: Yan
authors: Shinobu
authors: S
authors: Matsuura
authors: Christopher J
authors: CJ
authors: Hickey
authors: Miao-Chia
authors: MC
authors: Lo
authors: Wei-Jong
authors: WJ
authors: Shia
authors: Russell C
authors: RC
authors: DeKelver
authors: Dong-Er
authors: DE
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050989:GATA2 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006410:Hematopoiesis; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C552430:MIRN23a microRNA, human; C543845:MIRN24 microRNA, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; C534062:Mirn23b microRNA, mouse; C529080:Mirn24 microRNA, mouse; C540674:Mirn27 microRNA, mouse; D012333:RNA, Messenger; C088203:SON protein, human