期刊
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
卷 94, 期 -, 页码 10-21出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2017.11.002
关键词
RNA binding protein; Rbm24; RIP-Chip; Alternative splicing; Cardiomyocyte
资金
- National Natural Science Foundation of China (NSFC) [81670286]
- Major State Basic Research Development Program of China (973 program) [2014CB965101]
- Xiamen Joint Research Fund for Major Diseases [3502Z20159014]
- Shenzhen Free Exploration of Basic Research Fund [JCYJ20170306140656626]
- Xiamen Oceanic Administration [14PYY051SF04]
- Xiamen University
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.
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