Host translation is generally modulated by viral infection, including duck hepatitis A virus (DHAV) infection. Previously, we reported that cellular protein synthesis in a cell model of duck embryo fibroblasts is significantly inhibited by DHAV infection but not viral proteins, suggesting that an important viral-host interaction occurs at the translational level. In this study, we aim to further understand the impact of DHAV virulence on cellular N6-methyladenosine (m6A) modification, which is essential to a wide variety of RNA biological processes, such as mRNA stabilization and translation. Using m6A antibody-based immunoprecipitation, m6A-seq, and LC–MS/MS, we observed that m6A-modified mRNA exists in both virulent and attenuated DHAV-infected duckling livers. Importantly, m6A levels in mRNA were much higher in attenuated DHAV-infected livers compared with virulent DHAV-infected livers, suggesting virulence-dependent regulation of m6A modification. Analysis of modification motifs indicated that GAAGAAG is the most enriched motif. Combined m6A-seq and RNA-seq data analysis indicated a generally positive correlation between m6A and mRNA expression levels in DHAV-infected duckling livers. GO analysis of genes with decreased or increased m6A levels showed that these genes were enriched in various terms, including oxidation–reduction processes and antiviral immune responses. Collectively, our work reveals DHAV virulence-dependent coordination between m6A modification and mRNA expression in duckling livers.

10.3389/fimmu.2022.839677

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Nonstructural proteins 2B and 4A of Tembusu virus induce complete autophagy to promote viral multiplication in vitro

Veterinary Research (2023)

Wangyang Tan Senzhao Zhang Yu He Zhen Wu Mingshu Wang

Abstract Tembusu virus (TMUV) is an emerging flavivirus that has broken out in different regions of China. TMUV infection has been reported to induce autophagy in duck embryo fibroblast cells. However, the molecular mechanisms underlying this autophagy induction remain unclear. Here, we explored the interactions between autophagy and TMUV and the effects of the structural and nonstructural proteins of TMUV on autophagy in vitro. Among our results, TMUV infection enhanced autophagy to facilitate viral replication in HEK293T cells. After pharmacologically inducing autophagy with rapamycin (Rapa), the replication of TMUV increased by a maximum of 14-fold compared with the control group. To determine which TMUV protein primarily induced autophagy, cells were transfected with two structural proteins and seven nonstructural proteins of TMUV. Western blotting showed that nonstructural proteins 2B (NS2B) and 4 A (NS4A) of TMUV significantly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3) from LC3-I to LC3-II in HEK293T cells. In addition, through immunofluorescence assays, we found that NS2B and NS4A significantly increased the punctate fluorescence of GFP-LC3-II. Furthermore, we found that both NS2B and NS4A interacted with polyubiquitin-binding protein sequestosome 1 (SQSTM1/p62) in a coimmunoprecipitation assay. Moreover, the autophagic degradation of p62 and LC3 mediated by NS2B or NS4A was inhibited by treatment with the autophagic flux inhibitor chloroquine (CQ). These results confirmed the vital effects of NS2B and NS4A in TMUV-induced complete autophagy and clarified the importance of complete autophagy for viral replication, providing novel insight into the relationship between TMUV and autophagy.

HEK 293 cells

BAG3

10.1186/s13567-023-01152-2

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Supplementary Table S4 from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

Supplementary Table S4 shows p53LTCC lncRNAs (activated and repressed) associated with patient survival in prostate cancers.

10.1158/1541-7786.25964824

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Supplementary Figure S5 from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

Supplementary Figure S5 shows Kaplan Meier curves from TCGA cancer datasets

10.1158/1541-7786.25964839

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List of Supplementary Tables from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

List of Supplementary Tables with description of each table in the manuscript

10.1158/1541-7786.25964857

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Supplementary Table S1 from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

Supplementary Table S1 shows p53LTCC lncRNAs (activated and repressed) associated with patient survival in breast cancers.

10.1158/1541-7786.25964833.v1

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Supplementary Table S8 from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

Supplementary Table S8 shows publicly available ChIP-seq datasets pertaining to p53

10.1158/1541-7786.25964812.v1

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Supplementary Table S3 from Systematic Characterization of p53-Regulated Long Noncoding RNAs across Human Cancers Reveals Remarkable Heterogeneity among Different Tumor Types

Kausik Regunath Vitalay Fomin Zhaoqi Liu Pingzhang Wang Mainul Hoque

Supplementary Table S3 shows p53LTCC lncRNAs (activated and repressed) associated with patient survival in glioblastoma.

10.1158/1541-7786.25964827.v1

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The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κβ pathway

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Srimoyee Mukherjee Atish Barua Lu‐Yang Wang Bin Tian Claire Moore

Macrophages are required for our body's development and tissue repair and protect against microbial attacks. We previously reported a crucial role for regulation of mRNA 3'-end cleavage and polyadenylation (C/P) in monocyte to macrophage differentiation. The CFIm25 subunit of the C/P complex showed a striking increase upon differentiation of monocytes with Phorbol Myristate Acetate, suggesting that it promotes this process. To test this hypothesis, CFIm25 was overexpressed in two different monocytic cell lines, followed by differentiation. Both cell lines showed a significant increase in macrophage characteristics and an earlier slowing of the cell cycle. In contrast, depletion of CFIm25 hindered differentiation. Cell cycle slowing upon CFIm25 overexpression was consistent with a greater decrease in the proliferation markers PCNA and cyclin D1, coupled with increased 3'UTR lengthening of cyclin D1 mRNA. Since choice of other poly(A) sites could be affected by manipulating CFIm25, we identified additional genes with altered use of poly(A) sites during differentiation and examined how this changed upon CFIm25 overexpression. The mRNAs of positive regulators of NF-κB signaling, TAB2 and TBL1XR1, and NFKB1, which encodes the NF-κB p50 precursor, underwent 3'UTR shortening that was associated with increased protein expression compared to the control. Cells overexpressing CFIm25 also showed elevated levels of phosphorylated NF-κB-p65 and the NF-κB targets p21, Bcl-XL, ICAM1 and TNF-α at an earlier time and greater resistance to NF-κB chemical inhibition. In conclusion, our study supports a model in which CFIm25 accelerates the monocyte to macrophage transition by promoting alternative polyadenylation events which lead to activation of the NF-κB pathway.

Monocyte

10.1101/2024.09.03.611136

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Alternative polyadenylation of mRNA precursors

Nature Reviews Molecular Cell Biology (2016)

Bin Tian James L. Manley

Post-transcriptional modification

Precursor mRNA

RNA polymerase II

Transcription

10.1038/nrm.2016.116

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Citations (991)