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Exploring m6A and m5C Epitranscriptomes upon Viral Infection: an Example with HIV
Published on: March 5, 2022
Transcriptome-wide identification and analysis reveals m6A regulation of metabolic reprogramming in shrimp
Xumei Sun1, Yu-Lei Chen2, Fan Xin3
1School of Marine Sciences, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang Province, 315211, P. R. China.
Background:
It has been reported that the most common post-transcriptional modification of eukaryotic RNA is N6-methyladenosine (m6A). Previous studies show m6A is a key regulator for viral infection and immune response. However, whether there is a pathogen stimulus-dependent m6A regulation in invertebrate shrimp has not been studied.
Results:
In this study, we performed a transcriptome-wide profiling of mRNA m6A methylation in shrimp (Marsupenaeus japonicus) after white spot syndrome virus (WSSV) infection by methylated RNA immunoprecipitation sequencing (MeRIP-seq). A total of 15,436 m6A peaks were identified in the shrimp, distributed in 8,108 genes, mainly enriched in the CDS, 3' UTR region and near the stop codon. After WSSV infection, we identified 2,260 m6A peaks with significantly changes, of which 1,973 peaks were significantly up-regulated and 287 peaks were significantly down-regulated. 1,795 genes were identified as differentially methylated genes. GO and KEGG analysis showed that hyper-methylated genes or hypo-methylated genes were highly associated with innate immune process and related to metabolic pathways including HIF-1 signaling pathway, lysine degradation and Wnt signaling pathway. Combined analysis showed a positive correlation between m6A methylation levels and mRNA expression levels. In addition, computational predictions of protein-protein interaction indicated that genes with altered levels of m6A methylation and mRNA expression clustered in metabolism, DNA replication, and protein ubiquitination. ZC3H12A and HIF-1 were two hub genes in protein-protein interaction (PPI) network that involved in immune and metabolism processes, respectively.
Conclusion:
Our study explored the m6A methylation pattern of mRNA in shrimp after WSSV infection, exhibited the first m6A map of shrimp at the stage of WSSV induced metabolic reprogramming. These findings may reveal the possible mechanisms of m6A-mediated innate immune response in invertebrates.
Insights
This study reveals N6-methyladenosine (m6A) RNA modification patterns in shrimp post-white spot syndrome virus (WSSV) infection. It highlights m6A
Area of Science:
- Molecular Biology
- Immunology
- Genomics
Background:
- N6-methyladenosine (m6A) is the most common RNA post-transcriptional modification in eukaryotes.
- m6A plays a crucial role in viral infection and immune responses.
- Pathogen-driven m6A regulation in invertebrates like shrimp remains unstudied.
Purpose of the Study:
- To investigate the transcriptome-wide mRNA m6A methylation profile in shrimp following white spot syndrome virus (WSSV) infection.
- To identify changes in m6A methylation patterns and their association with immune and metabolic processes.
- To explore the role of m6A in the shrimp innate immune response to viral challenge.
Main Methods:
- Transcriptome-wide profiling of mRNA m6A methylation using methylated RNA immunoprecipitation sequencing (MeRIP-seq) in Marsupenaeus japonicus.
- Identification and analysis of m6A peaks and differentially methylated genes.
- Gene Ontology (GO) and KEGG pathway analysis, and protein-protein interaction (PPI) network construction.
Main Results:
- 15,436 m6A peaks were identified across 8,108 genes, primarily in CDS, 3' UTR, and near stop codons.
- WSSV infection induced significant changes in 2,260 m6A peaks (1,973 upregulated, 287 downregulated), affecting 1,795 genes.
- Differentially methylated genes were enriched in innate immunity and metabolic pathways (HIF-1, lysine degradation, Wnt signaling); m6A levels positively correlated with mRNA expression; ZC3H12A and HIF-1 emerged as key regulatory genes.
Conclusions:
- This study presents the first m6A map in shrimp during WSSV-induced metabolic reprogramming.
- Findings reveal pathogen stimulus-dependent m6A regulation in invertebrates.
- The results suggest potential mechanisms of m6A-mediated innate immunity in shrimp.
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