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.

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

“…More recently, studies have revealed that lncRNA can regulate the expression of key gene at various levels, such as epigenetic modification, transcription, and posttranscription, through a variety of mechanisms such as RNA‐RNA, RNA‐protein, and RNA‐DNA . Accumulating evidence has suggested that lncRNA binds to miRNAs in a competitive manner as a competitive endogenous RNA (ceRNA) to regulate gene expression, which is an important molecular mechanism of lncRNA involved in regulating the occurrence and development of diseases . Recent studies have demonstrated that specific lncRNAs share a close correlation with neural cell differentiation, synapses, elevated neuronal excitability, and neural network connection and remodeling, all of which suggest their possible involvement in the occurrence and development of epilepsy …”

“…7 Accumulating evidence has suggested that lncRNA binds to miRNAs in a competitive manner as a competitive endogenous RNA (ceRNA) to regulate gene expression, which is an important molecular mechanism of lncRNA involved in regulating the occurrence and development of diseases. 8,9 Recent studies have demonstrated that specific lncRNAs share a close correlation with neural cell differentiation, synapses, elevated neuronal excitability, and neural network connection and remodeling, all of which suggest their possible involvement in the occurrence and development of epilepsy. [10][11][12][13] MiRNAs represent a class of endogenous ncRNA encoded by the genome of higher eukaryotes with a length of about 22 nt.…”

NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found?

“…The role for NEAT1_1 in this process is less clear, however, it may potentiate NEAT1_2 function. A number of NEAT1-binding proteins, namely FUS, TDP-43, SFPQ and EWS, have been reported to modulate miRNA biogenesis [ [95] , [96] , [97] , [98] ].…”

COVID-19 Biomarkers in research: Extension of the OncoMX cancer biomarker data model to capture biomarker data from other diseases

“…Finally, our resource has also registered biomarkers like EWS, Cit-H3, and ACE2, that have extensive ramifications in various cancers. EWS, primarily implicated in Ewing’s Sarcoma, plays a role in transcriptional repression, and promotes tumorigenesis by forming fusion proteins 72 , 73 . Cit-H3 plays an important role in neutrophil release of nuclear chromatin, also called neutrophil extracellular traps (NETs), which have been associated with tumor progression in colon cancer 74 , 75 .…”