Defining an evolutionarily conserved role of GW182 in circular RNA degradation

Jia, Ruirui; Xiao, Mei-Sheng; Li, Zhengguo; Ge, Shengfang; Huang, Chuan

doi:10.1038/s41421-019-0113-y

Cited by 66 publications

(45 citation statements)

References 9 publications

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“…In addition, RBPs also regulate the degradation of circRNAs. For instance, GW182, a key component of P-body and RNAi machine, plays a crucial role in the process of circRNAs degradation through mediating the interactions between circRNAs and circRNA decay factors 52 . However, we found that the expression level of BCRC-3 was not affected by UBAC2 in this study.…”

Section: Discussionmentioning

confidence: 99%

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Zhao

Zhou

et al. 2020

Cell Death Dis

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Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan–Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3′UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

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Section: Discussionmentioning

confidence: 99%

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

Zhao

Zhou

et al. 2020

Cell Death Dis

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“…Another study found that the depletion of GW182 (a key component of the P-body and RNAi machine) resulted in the accumulation of endogenous circular transcripts. However, the depletion of other P-body components or RNAi complex factors did not have similar effects, indicating that GW182, not the P-body or RNAi machine, affected the degradation of circRNAs [88]. Regrettably, GW182 shows little effect on the nuclear export of circRNAs, and its functions in the cytoplasm has not been fully elucidated, so other studies are needed to explain the degradation of circRNA.…”

Section: A Modification Facilitates Circrna Degradationmentioning

confidence: 98%

The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs

et al. 2020

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N 6-methyladenosine (m 6 A), the most abundant modification in eukaryotic cells, regulates RNA transcription, processing, splicing, degradation, and translation. Circular RNA (circRNA) is a class of covalently closed RNA molecules characterized by universality, diversity, stability and conservatism of evolution. Accumulating evidence shows that both m 6 A modification and circRNAs participate in the pathogenesis of multiple diseases, such as cancers, neurological diseases, autoimmune diseases, and infertility. Recently, m 6 A modification has been identified for its enrichment and vital biological functions in regulating circRNAs. In this review, we summarize the role of m 6 A modification in the regulation and function of circRNAs. Moreover, we discuss the potential applications and possible future directions in the field.

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“…(ii) GW182: Using RNAi screening strategy, our group identified an evolutionarily conserved factor (GW182 in Drosophila; TNRC6A, TNRC6B, and TNRC6C in human) controls circular RNA stability in a P-body or AGO independent manner recently ( Figure 2). Surprisingly, the expression of parental linear RNAs were not affected upon GW182 depletion [19]. Although GW182's role in circular RNA stability control is yet to be identified, we hypothesize that GW182 might act as ae a molecular platform to recruit many decay factors, or GW182 might affect the subcellular localization of circular RNAs.…”

Section: Nuclear Exportmentioning

confidence: 84%

Circular RNAs in Brain Disorders

2019

Med One

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Circular RNAs, a class of covalently closed transcripts, are generated from thousands of protein-coding genes or noncoding regions of the genome via non-canonical splicing, and serve as important controllers in a variety of biological events in eukaryotes. Emerging studies have shown that circular RNAs are enriched in animal brains, and involved in brain disorders. In this review, we will discuss recent progress on circular RNA biogenesis, nuclear export, stability control, molecular functions, and regulatory roles in brain functions.

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Defining an evolutionarily conserved role of GW182 in circular RNA degradation

Cited by 66 publications

References 9 publications

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs

Circular RNAs in Brain Disorders

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