scholarly journals Caspases Switch off the m 6 A RNA Modification Pathway to Foster the Replication of a Ubiquitous Human Tumor Virus

mBio ◽  
2021 ◽  
Author(s):  
Kun Zhang ◽  
Yucheng Zhang ◽  
Yunash Maharjan ◽  
Febri Gunawan Sugiokto ◽  
Jun Wan ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Binding Proteins ◽  
Human Tumor ◽  
Rna Modification ◽  
Central Dogma ◽  
Tumor Virus

The discovery of an N 6 -methyladenosine (m 6 A) RNA modification pathway has fundamentally altered our understanding of the central dogma of molecular biology. This pathway is controlled by methyltransferases (writers), demethylases (erasers), and specific m 6 A binding proteins (readers).

scholarly journals Caspases switch off m6A RNA modification pathway to reactivate a ubiquitous human tumor virus

2020 ◽  
Author(s):  
Kun Zhang ◽  
Yucheng Zhang ◽  
Jun Wan ◽  
Renfeng Li
Keyword(s):  
Human Tumor ◽  
Feedback Regulation ◽  
Rna Modification ◽  
Barr Virus ◽  
Multiple Components ◽  
Tumor Virus ◽  
Epstein Barr ◽  
Caspase Substrate

AbstractThe methylation of RNA at the N6 position of adenosine (m6A) orchestrates multiple biological processes to control development, differentiation, and cell cycle, as well as various aspects of the virus life cycle. How the m6A RNA modification pathway is regulated to finely tune these processes remains poorly understood. Here, we discovered the m6A reader YTHDF2 as a caspase substrate via proteome-wide prediction, followed by in vitro and in vivo validations. We further demonstrated that cleavage-resistant YTHDF2 blocks, while cleavage-mimicking YTHDF2 fragments promote, the replication of a common human oncogenic virus, Epstein-Barr virus (EBV). Intriguingly, our study revealed a feedback regulation between YTHDF2 and caspase-8 via m6A modification of CASP8 mRNA and YTHDF2 cleavage during EBV replication. Further, we discovered that caspases cleave multiple components within the m6A RNA modification pathway to benefit EBV replication. Together, our study establishes that caspase disarming of the m6A RNA modification machinery fosters EBV reactivation.

DBP-PSSM: Combination of evolutionary profiles with the XGBoost algorithm to improve the identification of DNA-binding proteins

2020 ◽  
Vol 23 ◽  
Author(s):  
Yanping Zhang ◽  
Pengcheng Chen ◽  
Ya Gao ◽  
Jianwei Ni ◽  
Xiaosheng Wang
Keyword(s):  
Logistic Regression ◽  
Protein Structure ◽  
Dna Binding ◽  
Molecular Biology ◽  
Binding Proteins ◽  
Protein Sequences ◽  
Low Complexity ◽  
Dna Binding Proteins ◽  
Position Information ◽  
Position Representation

Aim and Objective:: Given the rapidly increasing number of molecular biology data available, computational methods of low complexity are necessary to infer protein structure, function, and evolution. Method:: In the work, we proposed a novel mthod, FermatS, which based on the global position information and local position representation from the curve and normalized moments of inertia, respectively, to extract features information of protein sequences. Furthermore, we use the generated features by FermatS method to analyze the similarity/dissimilarity of nine ND5 proteins and establish the prediction model of DNA-binding proteins based on logistic regression with 5-fold crossvalidation. Results:: In the similarity/dissimilarity analysis of nine ND5 proteins, the results are consistent with evolutionary theory. Moreover, this method can effectively predict the DNA-binding proteins in realistic situations. Conclusion:: The findings demonstrate that the proposed method is effective for comparing, recognizing and predicting protein sequences. The main code and datasets can download from https://github.com/GaoYa1122/FermatS.

EBV+ Lymphoproliferative Diseases: Opportunities for leveraging EBV as a Therapeutic Target

Blood ◽  
2021 ◽  
Author(s):  
Keri Toner ◽  
Catherine M. Bollard
Keyword(s):  
Proliferative Response ◽  
Epstein Barr Virus ◽  
Human Tumor ◽  
Lymphoproliferative Disease ◽  
Lymphoproliferative Diseases ◽  
Malignant Lymphomas ◽  
Barr Virus ◽  
Immune Therapies ◽  
Tumor Virus ◽  
Epstein Barr

Epstein-Barr virus (EBV) is a ubiquitous human tumor virus, which contributes to the development of lymphoproliferative disease, most notably in patients with impaired immunity. EBV associated lymphoproliferation is characterized by expression of latent EBV proteins and ranges in severity from a relatively benign proliferative response to aggressive malignant lymphomas. The presence of EBV can also serve as a unique target for directed therapies for the treatment of EBV lymphoproliferative diseases, including T cell based immune therapies. In this review, we will describe the EBV-associated lymphoproliferative diseases and will particularly focus on the therapies that target EBV.

Leukemia: A Second Human Tumor Virus

Science ◽  
1975 ◽  
Vol 187 (4174) ◽  
pp. 335-336 ◽  
Author(s):  
T. H. Maugh
Keyword(s):  
Human Tumor ◽  
Tumor Virus

scholarly journals Epstein-Barr Virus Facilitates Expression of KLF14 by Regulating the Cooperative Binding of the E2F-Rb-HDAC Complex in Latent Infection

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Yonggang Pei ◽  
Josiah Hiu-yuen Wong ◽  
Hem Chandra Jha ◽  
Tian Tian ◽  
Zhi Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Population ◽  
Regulatory Networks ◽  
Epstein Barr Virus ◽  
Latent Infection ◽  
Human Tumor ◽  
Barr Virus ◽  
Repressor Complex ◽  
Tumor Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) was discovered as the first human tumor virus more than 50 years ago. EBV infects more than 90% of the human population worldwide and is associated with numerous hematologic malignancies and epithelial malignancies. EBV establishes latent infection in B cells, which is the typical program seen in lymphomagenesis. Understanding EBV-mediated transcription regulatory networks is one of the current challenges that will uncover new insights into the mechanism of viral-mediated lymphomagenesis. Here, we describe the regulatory profiles of several cellular factors (E2F6, E2F1, Rb, HDAC1, and HDAC2) together with EBV latent nuclear antigens using next-generation sequencing (NGS) analysis. Our results show that the E2F-Rb-HDAC complex exhibits similar distributions in genomic regions of EBV-positive cells and is associated with oncogenic super-enhancers involving long-range regulatory regions. Furthermore, EBV latent antigens cooperatively hijack this complex to bind at KLFs gene loci and facilitate KLF14 gene expression in lymphoblastoid cell lines (LCLs). These results demonstrate that EBV latent antigens can function as master regulators of this multisubunit repressor complex (E2F-Rb-HDAC) to reverse its suppressive activities and facilitate downstream gene expression that can contribute to viral-induced lymphomagenesis. These results provide novel insights into targets for the development of new therapeutic interventions for treating EBV-associated lymphomas. IMPORTANCE Epstein-Barr virus (EBV), as the first human tumor virus, infects more than 90% of the human population worldwide and is associated with numerous human cancers. Exploring EBV-mediated transcription regulatory networks is critical to understand viral-associated lymphomagenesis. However, the detailed mechanism is not fully explored. Now we describe the regulatory profiles of the E2F-Rb-HDAC complex together with EBV latent antigens, and we found that EBV latent antigens cooperatively facilitate KLF14 expression by antagonizing this multisubunit repressor complex in EBV-positive cells. This provides potential therapeutic targets for the treatment of EBV-associated cancers.

Central Dogma of Molecular Biology

Nature ◽  
1970 ◽  
Vol 227 (5258) ◽  
pp. 561-563 ◽  
Author(s):  
FRANCIS CRICK
Keyword(s):  
Molecular Biology ◽  
Central Dogma

The Central Dogma of Molecular Biology

2005 ◽  
pp. 45
Author(s):  
Julia E. Richards ◽  
R. Scott Hawley
Keyword(s):  
Molecular Biology ◽  
Central Dogma

The impact of EBV on the epigenetics of gastric carcinoma

2020 ◽  
Author(s):  
Wen Liu ◽  
Bing Luo
Keyword(s):  
Gastric Carcinoma ◽  
Small Rnas ◽  
Human Tumor ◽  
Nuclear Antigen ◽  
Epigenetic Alterations ◽  
Latent Membrane Protein 2A ◽  
Viral Genes ◽  
Tumor Virus ◽  
The Impact

EBV is an important human tumor virus and is closely related to the occurrence of a variety of tumors, involving 10% of gastric cancer. In EBV-associated gastric carcinoma (EBVaGC), EBV expresses restrict viral genes including EBV nuclear antigen 1, EBV encoded small RNAs, Bam HI-A rightward transcripts, latent membrane protein 2A and miRNAs. The role of EBV in gastric carcinogenesis has received increasing attention and is considered to be another pathogenic factor in addition to Helicobacter pylori. A typical characteristic of EBVaGC is the extensive methylation of viral and host genome. Combined with other epigenetic mechanisms, EBV infection acts as an epigenetic driver of EBVaGC oncogenesis. In this review we discuss recent findings of EBV effect on host epigenetic alterations in EBVaGC and its role in oncogenic process.

scholarly journals DNA Tumor Viruses and Their Contributions to Molecular Biology

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
James M. Pipas
Keyword(s):  
Molecular Biology ◽  
Cancer Biology ◽  
Tumor Viruses ◽  
The World ◽  
Tumor Virus ◽  
History Of ◽  
The Impact

ABSTRACTThis summer marks the 51st anniversary of the DNA tumor virus meetings. Scientists from around the world will gather in Trieste, Italy, to report their latest results and to agree or disagree on the current concepts that define our understanding of this diverse class of viruses. This article offers a brief history of the impact the study of these viruses has had on molecular and cancer biology and discusses obstacles and opportunities for future progress.

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