Related Experiment Video
Updated: Jun 11, 2025
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
3.1K
EIF4A3 is stabilized by the long noncoding RNA BC200 to regulate gene expression during Epstein-Barr virus infection
Jing Li1,2,3,4, Yujie Xin1,2,3,4, Siwei Zhang1,2,3,5
1Department of Nuclear Medicine, Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Journal of Medical Virology
|October 7, 2024
Summary
Epstein-Barr virus (EBV) infection upregulates the long noncoding RNA BC200, which stabilizes the EIF4A3 protein. This BC200/EIF4A3 interaction impacts host gene expression, influencing viral infection and immune responses.
Area of Science:
- Molecular Biology
- Virology
- Epigenetics
Background:
- Epstein-Barr virus (EBV) infection modulates host gene expression for viral pathogenesis.
- Long noncoding RNAs (lncRNAs) are emerging as critical regulators in cellular processes.
- The role of lncRNAs in EBV-mediated host gene regulation was previously unclear.
Purpose of the Study:
- To investigate the role of lncRNAs in EBV infection.
- To identify novel regulatory mechanisms of host gene expression by EBV.
- To explore the function of eukaryotic initiation factor 4A3 (EIF4A3) in EBV-infected cells.
Main Methods:
- RNA immunoprecipitation and RNA pulldown assays to confirm BC200-EIF4A3 binding.
- Western blotting to assess protein level changes.
- RNA sequencing (RNA-seq) to analyze gene expression profiles after BC200 or EIF4A3 knockdown.
- Site-directed mutagenesis to identify key ubiquitination residues.
Main Results:
- BC200 expression is significantly upregulated in EBV-infected cells.
- BC200 directly binds to EIF4A3 and enhances its protein stability, not mRNA levels.
- BC200 protects EIF4A3 from K48-linked polyubiquitination at K195 and K198 residues.
- Knockdown of BC200 or EIF4A3 alters the expression of numerous host genes, particularly those in viral infection and immune response pathways.
Conclusions:
- This study reveals a novel regulatory axis, BC200/EIF4A3, by which EBV influences host gene expression.
- Identified key residues (K195, K198) in EIF4A3 protein ubiquitination.
- The findings provide insights into EBV pathogenesis and potential therapeutic targets for EBV-related diseases.
Related Concept Videos
02:28Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
01:53RNA Stability
33.3K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.3K
02:39lncRNA - Long Non-coding RNAs
8.5K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.5K
01:29Translational Regulation
5
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
5
01:23Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
02:31Nuclear Export of mRNA
7.6K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.6K