The Experts below are selected from a list of 15477 Experts worldwide ranked by ideXlab platform
Alessandro Rosa - One of the best experts on this subject based on the ideXlab platform.
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fus affects Circular RNA expression in murine embryonic stem cell derived motor neurons
Nature Communications, 2017Co-Authors: Alessandro Rosa, Lorenzo Errichelli, Stefano Dini Modigliani, Pietro Laneve, Ivano Legnini, Alessio Colantoni, Davide CapautoAbstract:The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS. The RNA binding protein FUS functions in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Here the authors show that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production in stem cell-derived motor neurons and that ALS-associated FUS mutations affect the biogenesis of circRNAs.
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fus affects Circular RNA expression in murine embryonic stem cell derived motor neurons
Nature Communications, 2017Co-Authors: Alessandro Rosa, Lorenzo Errichelli, Stefano Dini Modigliani, Pietro Laneve, Ivano Legnini, Alessio Colantoni, Davide CapautoAbstract:The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS.
Burton B Yang - One of the best experts on this subject based on the ideXlab platform.
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foxo3 activity promoted by non coding effects of Circular RNA and foxo3 pseudogene in the inhibition of tumor growth and angiogenesis
Oncogene, 2016Co-Authors: William W Du, Burton B Yang, Weining Yang, Xianmin LiAbstract:It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that Circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 Circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 Circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.
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foxo3 Circular RNA retards cell cycle progression via forming teRNAry complexes with p21 and cdk2
Nucleic Acids Research, 2016Co-Authors: William W Du, Preet Dhaliwal, Burton B Yang, Zhenguo Yang, Weining YangAbstract:Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include Circular RNAs, which include exonic Circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of Circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the Circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ-Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a teRNAry complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 teRNAry complex arrested the function of CDK2 and blocked cell cycle progression.
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foxo3 Circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses
European Heart Journal, 2016Co-Authors: Weining Yang, Burton B Yang, Zhenguo Yang, Yu Chen, Francis Stuart FosterAbstract:Aims Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a Circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches. Methods and results Using the approaches of molecular and cellular biology, we show that a Circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence. Doxorubicin-induced cardiomyopathy was aggravated by ectopic expression of circ-Foxo3 but was relieved by silencing endogenous circ-Foxo3. We also found that silencing circ-Foxo3 inhibited senescence of mouse embryonic fibroblasts and that ectopic expression of circ-Foxo3 induced senescence. We found that circ-Foxo3 was mainly distributed in the cytoplasm, where it interacted with the anti-senescent protein ID-1 and the transcription factor E2F1, as well as the anti-stress proteins FAK and HIF1α. Conclusion We conclude that ID-1, E2F1, FAK, and HIF1α interact with circ-Foxo3 and are retained in the cytoplasm and could no longer exert their anti-senescent and anti-stress roles, resulting in increased cellular senescence.
Lorenzo Errichelli - One of the best experts on this subject based on the ideXlab platform.
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fus affects Circular RNA expression in murine embryonic stem cell derived motor neurons
Nature Communications, 2017Co-Authors: Alessandro Rosa, Lorenzo Errichelli, Stefano Dini Modigliani, Pietro Laneve, Ivano Legnini, Alessio Colantoni, Davide CapautoAbstract:The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS. The RNA binding protein FUS functions in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Here the authors show that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production in stem cell-derived motor neurons and that ALS-associated FUS mutations affect the biogenesis of circRNAs.
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fus affects Circular RNA expression in murine embryonic stem cell derived motor neurons
Nature Communications, 2017Co-Authors: Alessandro Rosa, Lorenzo Errichelli, Stefano Dini Modigliani, Pietro Laneve, Ivano Legnini, Alessio Colantoni, Davide CapautoAbstract:The RNA-binding protein FUS participates in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Here we report that FUS controls back-splicing reactions leading to Circular RNA (circRNA) production. We identified circRNAs expressed in in vitro-derived mouse motor neurons (MNs) and determined that the production of a considerable number of these circRNAs is regulated by FUS. Using RNAi and overexpression of wild-type and ALS-associated FUS mutants, we directly correlate the modulation of circRNA biogenesis with alteration of FUS nuclear levels and with putative toxic gain of function activities. We also demonstrate that FUS regulates circRNA biogenesis by binding the introns flanking the back-splicing junctions and that this control can be reproduced with artificial constructs. Most circRNAs are conserved in humans and specific ones are deregulated in human-induced pluripotent stem cell-derived MNs carrying the FUSP525L mutation associated with ALS.
Weining Yang - One of the best experts on this subject based on the ideXlab platform.
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a Circular RNA circ dnmt1 enhances breast cancer progression by activating autophagy
Oncogene, 2018Co-Authors: Weining Yang, Zhenguo Yang, Faryal Mehwish Awan, Ling Fang, Juanjuan Lyu, Chun Peng, Sergey N Krylov, Yizhen XieAbstract:Circular RNAs are a large group of noncoding RNAs that are widely expressed in mammalian cells. Genome-wide analyses have revealed abundant and evolutionarily conserved Circular RNAs across species, which suggest specific physiological roles of these species. Using a microarray approach, we detected increased expression of a Circular RNA circ-Dnmt1 in eight breast cancer cell lines and in patients with breast carcinoma. Silencing circ-Dnmt1 inhibited cell proliferation and survival. Ectopic circ-Dnmt1 increased the proliferative and survival capacities of breast cancer cells by stimulating cellular autophagy. We found that circ-Dnmt1-mediated autophagy was essential in inhibiting cellular senescence and increasing tumor xenograft growth. We further found that ectopically expressed circ-Dnmt1 could interact with both p53 and AUF1, promoting the nuclear translocation of both proteins. Nuclear translocation of p53 induced cellular autophagy while AUF1 nuclear translocation reduced Dnmt1 mRNA instability, resulting in increased Dnmt1 translation. From here, functional Dnmt1 could then translocate into the nucleus, inhibiting p53 transcription. Computational algorithms revealed that both p53 and AUF1 could bind to different regions of circ-Dnmt1 RNA. Our results showed that the highly expressed Circular RNA circ-Dnmt1 could bind to and regulate oncogenic proteins in breast cancer cells. Thus circ-Dnmt1 appears to be an oncogenic Circular RNA with potential for further preclinical research.
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a Circular RNA binds to and activates akt phosphorylation and nuclear localization reducing apoptosis and enhancing cardiac repair
Theranostics, 2017Co-Authors: Zhenguo Yang, Weining Yang, Faryal Mehwish Awan, Yan Zeng, Chao ZhangAbstract:As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a Circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified in silico. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.
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foxo3 activity promoted by non coding effects of Circular RNA and foxo3 pseudogene in the inhibition of tumor growth and angiogenesis
Oncogene, 2016Co-Authors: William W Du, Burton B Yang, Weining Yang, Xianmin LiAbstract:It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that Circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 Circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 Circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.
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foxo3 Circular RNA retards cell cycle progression via forming teRNAry complexes with p21 and cdk2
Nucleic Acids Research, 2016Co-Authors: William W Du, Preet Dhaliwal, Burton B Yang, Zhenguo Yang, Weining YangAbstract:Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include Circular RNAs, which include exonic Circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of Circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the Circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ-Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a teRNAry complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 teRNAry complex arrested the function of CDK2 and blocked cell cycle progression.
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foxo3 Circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses
European Heart Journal, 2016Co-Authors: Weining Yang, Burton B Yang, Zhenguo Yang, Yu Chen, Francis Stuart FosterAbstract:Aims Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a Circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches. Methods and results Using the approaches of molecular and cellular biology, we show that a Circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence. Doxorubicin-induced cardiomyopathy was aggravated by ectopic expression of circ-Foxo3 but was relieved by silencing endogenous circ-Foxo3. We also found that silencing circ-Foxo3 inhibited senescence of mouse embryonic fibroblasts and that ectopic expression of circ-Foxo3 induced senescence. We found that circ-Foxo3 was mainly distributed in the cytoplasm, where it interacted with the anti-senescent protein ID-1 and the transcription factor E2F1, as well as the anti-stress proteins FAK and HIF1α. Conclusion We conclude that ID-1, E2F1, FAK, and HIF1α interact with circ-Foxo3 and are retained in the cytoplasm and could no longer exert their anti-senescent and anti-stress roles, resulting in increased cellular senescence.
Yong Peng - One of the best experts on this subject based on the ideXlab platform.
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Circular RNA f circsr derived from slc34a2 ros1 fusion gene promotes cell migration in non small cell lung cancer
Molecular Cancer, 2019Co-Authors: Ke Wu, Wenchen Pu, Jiankang Zhou, Youling Gong, Canhua Huang, Xun Liao, Juan He, Yong PengAbstract:Cancer-associated chromosomal translocations are reported to generate oncogenic Circular RNA (circRNA), contributing to tumorigenesis. The fusion gene SLC34A2-ROS1 (solute carrier family 34 member 2 and ROS proto-oncogene 1) plays an important role in non-small cell lung cancer (NSCLC) progression. However, whether SLC34A2-ROS1 gene can produce circRNA remains unknown. Here, we identified two novel circRNAs (F-circSR1 and F-circSR2) generated from SLC34A2-ROS1 fusion gene, while F-circSR1 has higher expression than F-circSR2. Functional studies through gain- and loss-of-function strategies showed that both F-circSRs promote cell migration in lung cancer cells, whereas they have little effect on cell proliferation. Using the minigene GFP reporter assay, we verified that the flanking complementary sequences with canonical splicing sites are essential for F-circSR biogenesis. Therefore, our findings demonstrate the oncogenic role of F-circSR in NSCLC and highlight its therapeutic potential.
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Circular RNA f circea 2a derived from eml4 alk fusion gene promotes cell migration and invasion in non small cell lung cancer
Molecular Cancer, 2018Co-Authors: Wenchen Pu, Youling Gong, Jiao Li, Yun Zhao, Yong PengAbstract:Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor-promoting Circular RNA (circRNA) generated from the back-splicing of EML4-ALK variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs produced from EML4-ALK gene and their roles in NSCLC are not well-characterized. Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring “AA” (rather than “AAAA” in F-circEA-4a) motif at the junction site. F-circEA-2a mainly locates in the cytoplasm and promotes cell migration and invasion, but has little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene, highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.