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The RNA binding protein EWS is broadly involved in the regulation of pri-miRNA processing in mammalian cells.


ABSTRACT: The Ewing Sarcoma protein (EWS) is a multifaceted RNA binding protein (RBP) with established roles in transcription, pre-mRNA processing and DNA damage response. By generating high quality EWS-RNA interactome, we uncovered its specific and prevalent interaction with a large subset of primary microRNAs (pri-miRNAs) in mammalian cells. Knockdown of EWS reduced, whereas overexpression enhanced, the expression of its target miRNAs. Biochemical analysis revealed that multiple elements in target pri-miRNAs, including the sequences flanking the stem-loop region, contributed to high affinity EWS binding and sequence swap experiments between target and non-target demonstrated that the flanking sequences provided the specificity for enhanced pri-miRNA processing by the Microprocessor Drosha/DGCR8. Interestingly, while repressing Drosha expression, as reported earlier, we found that EWS was able to enhance the recruitment of Drosha to chromatin. Together, these findings suggest that EWS may positively and negatively regulate miRNA biogenesis via distinct mechanisms, thus providing a new foundation to understand the function of EWS in development and disease.

SUBMITTER: Ouyang H 

PROVIDER: S-EPMC5716145 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The RNA binding protein EWS is broadly involved in the regulation of pri-miRNA processing in mammalian cells.

Ouyang Huiwu H   Zhang Kai K   Fox-Walsh Kristi K   Yang Yang Y   Zhang Chen C   Huang Jie J   Li Hairi H   Zhou Yu Y   Fu Xiang-Dong XD  

Nucleic acids research 20171201 21


The Ewing Sarcoma protein (EWS) is a multifaceted RNA binding protein (RBP) with established roles in transcription, pre-mRNA processing and DNA damage response. By generating high quality EWS-RNA interactome, we uncovered its specific and prevalent interaction with a large subset of primary microRNAs (pri-miRNAs) in mammalian cells. Knockdown of EWS reduced, whereas overexpression enhanced, the expression of its target miRNAs. Biochemical analysis revealed that multiple elements in target pri-m  ...[more]

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