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

Ngoc Tung Tran, Hairui Su, Alireza Khodadadi-Jamayran, Shan Lin, Li Zhang, Dewang Zhou, Kevin M. Pawlik, Tim M. Townes, Yabing Chen, James C. Mulloy, Xinyang Zhao

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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. Synopsis The lncRNA AS-RBM15 is transcriptionally up-regulated by RUNX1 and enhances RBM15 protein translation via its overlapping region with the RBM15 5′UTR. AS-RBM15 activated by the transcription factor RUNX1 promotes megakaryocyte differentiation via enhancing RBM15 protein translation. Exon 1 of AS-RBM15, which overlaps with the 5′UTR of RBM15 mRNA, is sufficient to enhance 5′cap-dependent RBM15 protein translation. The cytoplasmic fraction of AS-RBM15 is increased in response to megakaryocyte differentiation signals. The lncRNA AS-RBM15 is transcriptionally upregulated by RUNX1 and enhances RBM15 protein translation via its overlapping region with the RBM15 5′UTR.

Original languageEnglish (US)
Pages (from-to)887-900
Number of pages14
JournalEMBO Reports
Volume17
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • RBM15
  • antisense RNA
  • hematopoiesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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