The AS-RBM15 lncRNA enhances RBM15 protein translation during megakaryocyte differentiation.
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.
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Ngoc-Tung
NT
Tran
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Hairui
H
Su
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Alireza
A
Khodadadi-Jamayran
Cincinnati Children's Hospital, Cincinnati, OH, USA.
Shan
S
Lin
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Li
L
Zhang
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Dewang
D
Zhou
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Kevin M
KM
Pawlik
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Tim M
TM
Townes
Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA Research Department, Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.
Yabing
Y
Chen
Cincinnati Children's Hospital, Cincinnati, OH, USA.
James C
JC
Mulloy
Department of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA Zhaox88@uab.edu.
Xinyang
0000-0001-6677-7072
X
Zhao
D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism*; D014176:Protein Biosynthesis; D021381:Protein Transport; D016372:RNA, Antisense; D062085:RNA, Long Noncoding / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion; D014158:Transcription, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; C431574:RBM15 protein, human; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins
RBM15; antisense RNA; hematopoiesis