The AS-RBM15 lncRNA enhances RBM15 protein translation during megakaryocyte differentiation

EMBO Rep. 2016 Jun;17(6):887-900. doi: 10.15252/embr.201541970. Epub 2016 Apr 26.

Abstract

Antisense RNAs regulate the transcription and translation of the corresponding sense genes. Here, we report that an antisense RNA, AS-RBM15, is transcribed in the opposite direction within exon 1 of RBM15 RBM15 is a regulator of megakaryocyte (MK) differentiation and is also involved in a chromosome translocation t(1;22) in acute megakaryocytic leukemia. MK terminal differentiation is enhanced by up-regulation of AS-RBM15 expression and attenuated by AS-RBM15 knockdown. At the molecular level, AS-RBM15 enhances RBM15 protein translation in a CAP-dependent manner. The region of the antisense AS-RBM15 RNA, which overlaps with the 5'UTR of RBM15, is sufficient for the up-regulation of RBM15 protein translation. In addition, we find that transcription of both RBM15 and AS-RBM15 is activated by the transcription factor RUNX1 and repressed by RUNX1-ETO, a leukemic fusion protein. Therefore, AS-RBM15 is a regulator of megakaryocyte differentiation and may play a regulatory role in leukemogenesis.

Keywords: RBM15; antisense RNA; hematopoiesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Differentiation / genetics*
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Gene Expression
  • Gene Expression Regulation
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Megakaryocytes / cytology*
  • Megakaryocytes / metabolism*
  • Protein Biosynthesis
  • Protein Transport
  • RNA, Antisense*
  • RNA, Long Noncoding / genetics*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism*
  • Sequence Deletion
  • Transcription, Genetic

Substances

  • Core Binding Factor Alpha 2 Subunit
  • RBM15 protein, human
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA-Binding Proteins