scholarly journals c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Bingyan Li ◽  
Guang Zhang ◽  
Zhongyu Wang ◽  
Yang Yang ◽  
Chenfeng Wang ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Messenger Rna ◽  
Untranslated Region ◽  
Rna Binding ◽  
Noncoding Rnas ◽  
Negative Regulator ◽  
Cancer Initiation ◽  
Important Player ◽  
Oncogenic Function ◽  
Transcriptional Target

AbstractThe c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3′-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function.

scholarly journals 7SL RNA represses p53 translation by competing with HuR

2014 ◽  
Vol 42 (15) ◽  
pp. 10099-10111 ◽  
Author(s):  
Kotb Abdelmohsen ◽  
Amaresh C Panda ◽  
Min-Ju Kang ◽  
Rong Guo ◽  
Jiyoung Kim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Untranslated Region ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Transcriptional Regulators ◽  
Tumor Suppressor P53 ◽  
P53 Expression ◽  
7Sl Rna ◽  
Partial Hybrid

Abstract Noncoding RNAs (ncRNAs) and RNA-binding proteins are potent post-transcriptional regulators of gene expression. The ncRNA 7SL is upregulated in cancer cells, but its impact upon the phenotype of cancer cells is unknown. Here, we present evidence that 7SL forms a partial hybrid with the 3′-untranslated region (UTR) of TP53 mRNA, which encodes the tumor suppressor p53. The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes. Silencing 7SL led to increased binding of HuR to TP53 mRNA, an interaction that led to the promotion of p53 translation and increased p53 abundance. We propose that the competition between 7SL and HuR for binding to TP53 3′UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53. Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels.

scholarly journals Long Noncoding RNAs and RNA-Binding Proteins in Oxidative Stress, Cellular Senescence, and Age-Related Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-21 ◽  
Author(s):  
Chongtae Kim ◽  
Donghee Kang ◽  
Eun Kyung Lee ◽  
Jae-Seon Lee
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Age Related ◽  
Complex Biological Process

Cellular senescence is a complex biological process that leads to irreversible cell-cycle arrest. Various extrinsic and intrinsic insults are associated with the onset of cellular senescence and frequently accompany genomic or epigenomic alterations. Cellular senescence is believed to contribute to tumor suppression, immune response, and tissue repair as well as aging and age-related diseases. Long noncoding RNAs (lncRNAs) are >200 nucleotides long, poorly conserved, and transcribed in a manner similar to that of mRNAs. They are tightly regulated during various cellular and physiological processes. Although many lncRNAs and their functional roles are still undescribed, the importance of lncRNAs in a variety of biological processes is widely recognized. RNA-binding proteins (RBPs) have a pivotal role in posttranscriptional regulation as well as in mRNA transport, storage, turnover, and translation. RBPs interact with mRNAs, other RBPs, and noncoding RNAs (ncRNAs) including lncRNAs, and they are involved in the regulation of a broad spectrum of cellular processes. Like other cell fate regulators, lncRNAs and RBPs, separately or cooperatively, are implicated in initiation and maintenance of cellular senescence, aging, and age-related diseases. Here, we review the current understanding of both lncRNAs and RBPs and their association with oxidative stress, senescence, and age-related diseases.

scholarly journals Application of the 3'-Untranslated Region of Messenger RNA from Measles Virus Matrix Protein as an RNA Stabilizer: Implications in Pharmaceutical Biotechnology

2019 ◽  
Vol 9 (1) ◽  
pp. 53
Author(s):  
Marzieh Marzbany ◽  
Fatemeh Ghassemi ◽  
Mahsa Rasekhian
Keyword(s):  
Mrna Stability ◽  
Messenger Rna ◽  
Untranslated Region ◽  
Measles Virus ◽  
Matrix Protein ◽  
Rna Binding ◽  
Rna Stability ◽  
Minimum Free Energy ◽  
Expression Vectors ◽  
Dependent Manner

BACKGROUND: The market for the use of recombinant proteins for medical applications has been increasing in recent years. In many cases including fast production of significant amounts of protein for research purposes, transient transfection is the method of choice. In this regard expression vectors are one of the decisive factors in the cost-effectiveness of the production process. The genetic elements found in the 3’untranslated region (UTR) of mRNA expressed by such vectors, play an essential role in determining its stability and thus in the efficiency of the process. METHODS: In this study, the 3'UTR of matrix protein from the Measles Virus (MV) was used to construct a reporter plasmid containing Enhanced Green Fleurocent Protein (EGFP). The reporter construct was transfected into three cell lines. The effect of 3'UTR on mRNA stability was evaluated by real-time PCR. Secondary structure of the mrna was predicted based on minimum free energy. 3'UTR was analyzed in silico for the presence of binding motifs for trans-acting elements with known effects on RNA stability. RESULTS: Addition of 3’UTR of MV matrix protein sequence to the 3’ end of the mRNA, increased the EGFP- mRNA stability in time and cell-dependent manner. Analysis for the presence of known cis-acting motifs in 3’UTR indicated the presence of two PABPC1 binding sites, an RNA-binding protein, known for its stability and translation enhancing effects. CONCLUSION: Our results verified the potential of the 3'UTR region of matrix protein mRNA for improvement of transient recombinant protein production and vector design for mammalian cell hosts.

scholarly journals Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Diwen Zhang ◽  
Zhigang Zhou ◽  
Ruixia Yang ◽  
Sujun Zhang ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Immunity ◽  
Messenger Rna ◽  
Untranslated Region ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Related Proteins ◽  
Potential Tumor Suppressor

Tristetraprolin (TTP), a well-known RNA-binding protein, primarily affects the expression of inflammation-related proteins by binding to the targeted AU-rich element in the 3’ untranslated region after transcription and subsequently mediates messenger RNA decay. Recent studies have focused on the role of TTP in tumors and their related microenvironments, most of which have referred to TTP as a potential tumor suppressor involved in regulating cell proliferation, apoptosis, and metastasis of various cancers, as well as tumor immunity, inflammation, and metabolism of the microenvironment. Elevated TTP expression levels could aid the diagnosis and treatment of different cancers, improving the prognosis of patients. The aim of this review is to describe the role of TTP as a potential safeguard against carcinoma.

scholarly journals The Nuclear Exosome Contributes to Autogenous Control of NAB2 mRNA Levels

2005 ◽  
Vol 25 (5) ◽  
pp. 1577-1585 ◽  
Author(s):  
Kelly M. Roth ◽  
Maria K. Wolf ◽  
Marie Rossi ◽  
J. Scott Butler
Keyword(s):  
Rna Processing ◽  
Untranslated Region ◽  
Rna Binding ◽  
Noncoding Rnas ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Autogenous Control ◽  
Regulatory Circuit ◽  
Mrna Surveillance ◽  
Nuclear Exosome

ABSTRACT The RNA-processing exosome is a complex of riboexonucleases required for 3′-end formation of some noncoding RNAs and for the degradation of mRNAs in eukaryotes. The nuclear form of the exosome functions in an mRNA surveillance pathway that retains and degrades improperly processed precursor mRNAs within the nucleus. We report here that the nuclear exosome controls the level of NAB2 mRNA, encoding the nuclear poly(A)+-RNA-binding protein Nab2p. Mutations affecting the activity of the nuclear, but not the cytoplasmic, exosome cause an increase in the amount of NAB2 mRNA. Cis- and trans-acting mutations that inhibit degradation by the nuclear-exosome subunit Rrp6p result in elevated levels of NAB2 mRNA. Control of NAB2 mRNA levels occurs posttranscriptionally and requires a sequence of 26 consecutive adenosines (A26) in the NAB2 3′ untranslated region, which represses NAB2 3′-end formation and sensitizes the transcript to degradation by Rrp6p. Analysis of NAB2 mRNA levels in a nab2-1 mutant and in the presence of excess Nab2p indicates that Nab2p activity negatively controls NAB2 mRNA levels in an A26- and Rrp6p-dependent manner. These findings suggest a novel regulatory circuit in which the nuclear exosome controls the level of NAB2 mRNA in response to changes in the activity of Nab2 protein.

scholarly journals Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis

2019 ◽  
Vol 116 (29) ◽  
pp. 14620-14629 ◽  
Author(s):  
Chenfeng Wang ◽  
Yang Yang ◽  
Guang Zhang ◽  
Jingxin Li ◽  
Xianning Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Long Noncoding Rna ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Cell Cycle Control ◽  
Intrinsic Nature ◽  
Important Player ◽  
E2f1 Expression

Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.

PlncRNADB: A Repository of Plant lncRNAs and lncRNA-RBP Protein Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Noncoding Rnas ◽  
Reference Database ◽  
Protein Coding ◽  
Arabidopsis Lyrata ◽  
User Friendly

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.

scholarly journals Asymmetric reconstruction of mammalian reovirus reveals interactions among RNA, transcriptional factor µ2 and capsid proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Muchen Pan ◽  
Ana L. Alvarez-Cabrera ◽  
Joon S. Kang ◽  
Lihua Wang ◽  
Chunhai Fan ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Molecular Interactions ◽  
Messenger Rna ◽  
Rna Binding ◽  
Capsid Proteins ◽  
Rna Transcription ◽  
Infectious Particle ◽  
Virion Assembly ◽  
Rna Capping

AbstractMammalian reovirus (MRV) is the prototypical member of genus Orthoreovirus of family Reoviridae. However, lacking high-resolution structures of its RNA polymerase cofactor μ2 and infectious particle, limits understanding of molecular interactions among proteins and RNA, and their contributions to virion assembly and RNA transcription. Here, we report the 3.3 Å-resolution asymmetric reconstruction of transcribing MRV and in situ atomic models of its capsid proteins, the asymmetrically attached RNA-dependent RNA polymerase (RdRp) λ3, and RdRp-bound nucleoside triphosphatase μ2 with a unique RNA-binding domain. We reveal molecular interactions among virion proteins and genomic and messenger RNA. Polymerase complexes in three Spinoreovirinae subfamily members are organized with different pseudo-D3d symmetries to engage their highly diversified genomes. The above interactions and those between symmetry-mismatched receptor-binding σ1 trimers and RNA-capping λ2 pentamers balance competing needs of capsid assembly, external protein removal, and allosteric triggering of endogenous RNA transcription, before, during and after infection, respectively.

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