Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer

Tang, Yue; Wang, Jinpeng; Yu, Li; Fan, Chongxi; Zhang, Ping; Wu, Yingfen; Li, Xiayu; Xiong, Fang; Li, Xiaoling; Li, Guiyuan; Xiong, Wei; Zeng, Zhaoyang

doi:10.1186/s12943-017-0612-0

Cited by 122 publications

(89 citation statements)

References 57 publications

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“…Elution profiles show these core subunits co-elute with PBAF-only subunits in the control, but co-elute with BAF-only subunits upon RNA degradation ( Figure S6). These data suggest BAF exists as a non-RNA-associated complex while PBAF functions as an RNP complex, consistent with its known role in transcription and supporting a previously described RNA-binding model where lncRNAs interact with SWI/SNF complexes in cancer (Tang et al, 2017). Together, these examples demonstrate the power of DIF-FRAC to describe the various physical relationships between RNA and macromolecular protein complexes.…”

Section: Classification Of Rnp Complexessupporting

confidence: 86%

“…10! SWI/SNF-B) complexes as compositional RNP complexes, which is significant because these are some of the most frequently mutated protein complexes in cancer (Hodges et al, 2016;Tang et al, 2017) (Figure S6). BAF and PBAF complexes share a set of common core subunits, but also each have signature subunits that are related to their respective functions.…”

Section: Classification Of Rnp Complexesmentioning

confidence: 99%

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Systematic discovery of endogenous human ribonucleoprotein complexes

Mallam

Sae-Lee

Schaub

et al. 2018

Preprint

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RNA-binding proteins (RBPs) play essential roles in biology and are frequently associated with human disease. While recent studies have systematically identified individual RBPs, their higher order assembly into Ribonucleoprotein (RNP) complexes has not been systematically investigated. Here, we describe a proteomics method for systematic identification of RNP complexes in human cells. We identify 1,428 protein complexes that associate with RNA, indicating that over 20% of known human protein complexes contain RNA. To explore the role of RNA in the assembly of each complex, we identify complexes that dissociate, change composition, or form stable protein-only complexes in the absence of RNA. Importantly, these data also provide specific novel insights into the function of well-studied protein complexes not previously known to associate with RNA, including replication factor C (RFC) and cytokinetic centralspindlin complex. Finally, we use our method to systematically identify cell-type specific RNA-associated proteins in mouse embryonic stem cells. We distribute these data as a resource, rna.MAP (rna.proteincomplexes.org) which provides a comprehensive dataset for the study of RNA-associated protein complexes. Our system thus provides a novel methodology for further explorations across human tissues and disease states, as well as throughout all domains of life. ! 3! ! 4! upon CF-MS by comparing chromatographic separations of cellular lysate under control and RNA degrading conditions ( Figure 1A). A statistical framework is then applied to discover RNP complexes by identifying concurrent shifts of known protein complex subunits upon RNA degradation ( Figure 1A).Analysis of DIF-FRAC data answers important questions as to the role of RNA plays in macromolecular complexes. Specifically, we identify RNP complexes that 1) dissociate, 2) form stable protein-only complexes, and 3) change composition in the absence of RNA suggesting specific roles for RNA in each of these cases. Because DIF-FRAC is independent of UV crosslinking, nucleotide incorporation, genetic manipulation or poly(A) RNA capture efficiency, it can therefore be used to investigate a wide variety of cell types, tissues and species. To demonstrate this versatility, we apply DIF-FRAC to mouse embryonic stem cells (mESCs), identifying 1,165 RNA-associated proteins, to show the method is highly adaptable and can be extended to discover RNP complexes in diverse samples.Finally, we created a system-wide resource of 1,428 RNP complexes, many of which are previously unreported as having an RNA component, representing 20% of known human protein complexes. We provide our resource, rna.MAP, to the community as a fully searchable web database at rna.proteincomplexes.org. Results and Discussion Differential fractionation (DIF-FRAC) identifies RNP complexesThe DIF-FRAC strategy builds upon our previous strategy of Co-Fractionation Massspectroscopy (CF-MS) for identifying protein complexes in cellular lysate (Havugimana et al., 2012;Wan et al., 2015). CF-MS chromatograp...

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Section: Classification Of Rnp Complexessupporting

confidence: 86%

Section: Classification Of Rnp Complexesmentioning

confidence: 99%

Systematic discovery of endogenous human ribonucleoprotein complexes

Mallam

Sae-Lee

Schaub

et al. 2018

Preprint

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“…However, due to the latency of EBV infection, the virus might not be detected in some patients, and false positives are often observed. Some RNAs, including noncoding RNAs and miRNAs, can also function as serum markers, but are unstable in serum. Because of the unique structure of circRNAs, they can be delivered by exosomes and are more stable in serum than circulating tumor DNAs or RNAs.…”

Section: Discussionmentioning

confidence: 99%

circMAN1A2 could serve as a novel serum biomarker for malignant tumors

et al. 2019

Self Cite

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Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real‐time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.

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“…Additionally, lncRNAs can act as sRNA sponges and stabilize mRNA Lister et al, 2017). As previously stated, lncRNA can also guide nucleosome remodeling proteins to targeted genomic regions (Tang et al, 2017). Finally, lncRNAs have been demonstrated to be regulators of glucose homeostasis and their dysregulation has been linked to the pathogenesis and progression of diabetes (Gao et al, 2014;Petry et al, 2010).…”

Section: Rna-mediated Chromatin Regulationmentioning

confidence: 92%

Chromatin modifications in metabolic disease: Potential mediators of long‐term disease risk

Costello

Schones

2018

WIREs Mechanisms of Disease

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Metabolic diseases such as obesity and diabetes are complex diseases resulting from multiple genetic and environmental factors, such as diet and activity levels. These factors are well known contributors to the development of metabolic diseases. One manner by which environmental factors can influence metabolic disease progression is through modifications to chromatin. These modifications can lead to altered gene regulatory programs, which alters disease risk. Furthermore, there is evidence that parents exposed to environmental factors can influence the metabolic health of offspring, especially if exposures are during intrauterine growth periods. In this Review, we outline the evidence that chromatin modifications are associated with metabolic diseases, including diabetes and obesity. We also consider evidence that these chromatin modifications can lead to long-term disease risk and contribute to disease risk for future generations.

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Linking long non-coding RNAs and SWI/SNF complexes to chromatin remodeling in cancer

Cited by 122 publications

References 57 publications

Systematic discovery of endogenous human ribonucleoprotein complexes

Systematic discovery of endogenous human ribonucleoprotein complexes

circMAN1A2 could serve as a novel serum biomarker for malignant tumors

Chromatin modifications in metabolic disease: Potential mediators of long‐term disease risk

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