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J Biol Chem. 2013 Feb 22;288(8):5381-8. doi: 10.1074/jbc.M112.447227. Epub 2013 Jan 14.

SON protein regulates GATA-2 through transcriptional control of the microRNA 23a~27a~24-2 cluster.

Author information

1
Moores UCSD Cancer Center, the University of California San Diego, La Jolla, California 92093, USA.

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.

PMID:
23322776
PMCID:
PMC3581430
DOI:
10.1074/jbc.M112.447227
[Indexed for MEDLINE]
Free PMC Article
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