Document Detail


SON protein regulates GATA-2 through transcriptional control of the microRNA 23a~27a~24-2 cluster.
MedLine Citation:
PMID:  23322776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Erin Eun-Young Ahn; Tsunehito Higashi; Ming Yan; Shinobu Matsuura; Christopher J Hickey; Miao-Chia Lo; Wei-Jong Shia; Russell C DeKelver; Dong-Er Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-04-25     Revised Date:  2014-02-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5381-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions
Animals
Cell Differentiation
DNA-Binding Proteins / genetics,  physiology*
GATA2 Transcription Factor / metabolism*
Gene Expression Regulation*
Hematopoiesis
Humans
K562 Cells
Leukemia, Myeloid, Acute / metabolism
Mice
Mice, Inbred C57BL
MicroRNAs / metabolism*
Models, Biological
Promoter Regions, Genetic
RNA Splicing
RNA, Messenger / metabolism
U937 Cells
Up-Regulation
Grant Support
ID/Acronym/Agency:
CA096735/CA/NCI NIH HHS; F32 HL091641/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/DNA-Binding Proteins; 0/GATA2 Transcription Factor; 0/MIRN23 microRNA, human; 0/MIRN24 microRNA, human; 0/MIRN27 microRNA, human; 0/MicroRNAs; 0/Mirn23b microRNA, mouse; 0/Mirn24 microRNA, mouse; 0/Mirn27 microRNA, mouse; 0/RNA, Messenger; 0/SON protein, human
Comments/Corrections

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