Role of RNA Modifications in tRNA Structural Stability and Accurate Protein Synthesis

Abstract The present study evaluated the mechanism by which protein synthesis inhibitors activate bovine oocytes. The aim was to analyze the dynamics of MPF and MAPKs. MII oocytes were activated with ionomycin (Io), ionomycin+anisomycin (ANY) and ionomycin+cycloheximide (CHX) and by in vitro fertilization (IVF). The expression of cyclin B1, p-CDK1, p-ERK1/2, p-JNK, and p-P38 were evaluated by immunodetection and the kinase activity of ERK1/2 was measured by enzyme assay. Evaluations at 1, 4, and 15 hours postactivation (hpa) showed that the expression of cyclin B1 was not modified by the treatments. ANY inactivated MPF by p-CDK1Thr14-Tyr15 at 4 hpa (P < 0.05), CHX increased pre-MPF (p-CDK1Thr161 and p-CDK1Thr14-Tyr15) at 1 hpa and IVF increased p-CDK1Thr14-Tyr15 at 17 hours postfertilization (hpf) (P < 0.05). ANY and CHX reduced the levels of p-ERK1/2 at 4 hpa (P < 0.05) and its activity at 4 and 1 hpa, respectively (P < 0.05). Meanwhile, IVF increased p-ERK1/2 at 6 hpf (P < 0.05); however, its kinase activity decreased at 6 hpf (P < 0.05). p-JNK in ANY, CHX, and IVF oocytes decreased at 4 hpa (P < 0.05). p-P38 was only observed at 1 hpa, with no differences between treatments. In conclusion, activation of bovine oocytes by ANY, CHX, and IVF inactivates MPF by CDK1-dependent specific phosphorylation without cyclin B1 degradation. ANY or CHX promoted this inactivation, which seemed to be more delayed in the physiological activation (IVF). Both inhibitors modulated MPF activity via an ERK1/2-independent pathway, whereas IVF activated the bovine oocytes via an ERK1/2-dependent pathway. Finally, ANY does not activate the JNK and P38 kinase pathways.

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The Role of Adenosine Triphosphate Deficiency in Ethionine-induced Inhibition of Protein Synthesis

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)81133-4 ◽

1963 ◽

Vol 238 (5) ◽

pp. 1757-1763

Author(s):

Saul Villa-Trevino ◽

Kenneth H. Shull ◽

Emmanuel Farber

Keyword(s):

Protein Synthesis ◽

Adenosine Triphosphate ◽

Inhibition Of Protein Synthesis

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Studies on the role of RNA and protein synthesis in the lipolytic action of growth hormone in isolated fat cells

Advances in Enzyme Regulation ◽

10.1016/0065-2571(67)90007-6 ◽

1967 ◽

Vol 5 ◽

pp. 39-51 ◽

Cited By ~ 27

Author(s):

John N. Fain

Keyword(s):

Growth Hormone ◽

Protein Synthesis ◽

Fat Cells ◽

Isolated Fat Cells ◽

Lipolytic Action ◽

Rna And Protein Synthesis

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Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma

Genome Biology ◽

10.1186/s13059-021-02308-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Jie Yu ◽

Peiwei Chai ◽

Minyue Xie ◽

Shengfang Ge ◽

Jing Ruan ◽

...

Keyword(s):

Macrophage Polarization ◽

Regulation Of Gene Expression ◽

Metabolic Stress ◽

Ocular Melanoma ◽

Rna Modifications ◽

M1 Macrophage ◽

Melanoma Therapy

Abstract Background Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear. Results Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma. Conclusion We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.

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Recovery of beta-adrenergic receptors following long term exposure of astrocytoma cells to catecholamine. Role of protein synthesis.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)43267-x ◽

1981 ◽

Vol 256 (23) ◽

pp. 12281-12286 ◽

Cited By ~ 4

Author(s):

R.C. Doss ◽

J.P. Perkins ◽

T.K. Harden

Keyword(s):

Protein Synthesis ◽

Adrenergic Receptors ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Astrocytoma Cells

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MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03973-5 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Peng Xia ◽

Hao Zhang ◽

Kequan Xu ◽

Xiang Jiang ◽

Meng Gao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

P53 Protein ◽

Rna Modifications ◽

M Cell ◽

Mesenchymal Transition ◽

Akt Phosphorylation ◽

Repeat Domain ◽

Cell Cycle Transition

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

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