Global profiling of Rbm24 bound RNAs uncovers a multi-tasking RNA binding protein

被引:15
作者
Lin, Yu [1 ]
Tan, Kar Tong [2 ]
Liu, Jing [1 ]
Kong, Xu [1 ]
Huang, Zhengrong [4 ]
Xu, Xiu Qin [1 ,3 ]
机构
[1] Xiamen Univ, Inst Stem Cell & Regenerat Med, Coll Med, Chengzhi Bldg,Xiangan Campus, Xiamen 361100, Fujian, Peoples R China
[2] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore
[3] Xiamen Univ, ShenZhen Res Inst, Xiamen, Peoples R China
[4] Xiamen Univ, Affiliated Hosp 1, Dept Cardiol, Xiamen 361000, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
RNA binding protein; Rbm24; RIP-Chip; Alternative splicing; Cardiomyocyte; FAMILIAL DILATED CARDIOMYOPATHY; MYC MESSENGER-RNA; CODING-REGION; MYOGENIC DIFFERENTIATION; IN-VITRO; GENE; EXPRESSION; MICE; IDENTIFICATION; CELLS;
D O I
10.1016/j.biocel.2017.11.002
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
RNA binding proteins serve as critical molecular switches in a multitude of post-transcriptional regulatory processes. In the heart and muscles, the tissue specific RNA binding protein, Rbm24, is known to play important developmental roles via driving different post-transcriptional processes. Nonetheless, the currently identified molecular targets and regulatory pathways seem inadequate to completely explain the observed developmental effects upon Rbm24 knockdown/knockout. Here, by performing RNA Immunoprecipitation and coupling it to microarrays (RIP-Chip), we have generated an atlas of the mRNA binding repertoire of Rbm24. Further functional evaluation of its targets led to the elucidation of novel roles for Rbm24 in post-transcriptional processing, besides its already known roles in regulation of mRNA stability and alternative splicing. Interestingly, Rbm24 is found to cause the destabilization of Chrm2 via binding to an element in the coding region. In addition, Rbm24 is also found to have an uncharacterized role in driving the generation of isoforms with alternative transcriptional start sites. We have, for the first time, demonstrated that Rbm24 is a multi-tasking RNA binding protein capable of regulating its bound targets via a range of mechanisms.
引用
收藏
页码:10 / 21
页数:12
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