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Rbm15 modulates Notch-induced transcriptional activation and affects myeloid differentiation

Xianyong Ma1, Matthew J Renda, Lin Wang

  • 1Yale University School of Medicine, Department of Laboratory Medicine, P.O. Box 208035, 333 Cedar Street, New Haven, CT 06520-8035, USA.

Molecular and Cellular Biology
|February 7, 2007
PubMed

Insights

The RBM15 protein plays a key role in myelopoiesis, regulating myeloid cell differentiation. It influences Notch signaling, potentially inhibiting differentiation in hematopoietic cells.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cellular Differentiation

Background:

  • RBM15 (RNA-binding protein 15) is a known fusion partner in acute megakaryoblastic leukemia.
  • Understanding the normal function of RBM15 is crucial for elucidating its role in leukemia.

Purpose of the Study:

  • To investigate the normal function of RBM15 in myelopoiesis.
  • To determine the mechanism by which RBM15 influences hematopoietic cell differentiation.

Main Methods:

  • RNA interference (RNAi) to decrease RBM15 levels.
  • Enforced expression of RBM15.
  • Analysis of Notch-induced HES1 promoter activity.
  • Coimmunoprecipitation assays to study protein interactions.

Main Results:

  • Rbm15 is highly expressed in hematopoietic stem cells and during myelopoiesis.
  • Decreased Rbm15 enhances myeloid precursor cell differentiation, while enforced expression inhibits it.
  • Rbm15 differentially regulates Notch-induced HES1 transcription in hematopoietic versus nonhematopoietic cells.
  • The N-terminus of Rbm15 interacts with RBPJkappa and can inhibit HES1 promoter activity.

Conclusions:

  • Rbm15 is differentially expressed during hematopoiesis.
  • Rbm15 may inhibit myeloid differentiation by stimulating Notch signaling through RBPJkappa in hematopoietic cells.

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