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

被引：77

作者：

Ngoc-Tung Tran ^{[1
]}

Su, Hairui ^{[1
]}

Khodadadi-Jamayran, Alireza ^{[1
]}

Lin, Shan ^{[2
]}

Zhang, Li ^{[1
]}

Zhou, Dewang ^{[1
]}

Pawlik, Kevin M. ^{[1
]}

Townes, Tim M. ^{[1
]}

Chen, Yabing ^{[3
,4
]}

Mulloy, James C. ^{[2
]}

Zhao, Xinyang ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Dept Biochem & Mol Genet, Birmingham, AL 35233 USA

[2] Cincinnati Childrens Hosp, Cincinnati, OH USA

[3] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[4] Birmingham Vet Affairs Med Ctr, Res Dept, Birmingham, AL USA

来源：

EMBO REPORTS | 2016年 / 17卷 / 06期

关键词：

antisense RNA; hematopoiesis; RBM15; LONG NONCODING RNAS; NATURAL ANTISENSE TRANSCRIPT; HEMATOPOIETIC STEM-CELLS; GENOME-WIDE ANALYSIS; MESSENGER-RNA; C-MYC; GENE; RUNX1; SENSE; EXPRESSION;

D O I：

10.15252/embr.201541970

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：887 / 900

页数：14

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